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Medical Immunology

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Articles 1831 - 1860 of 2005

Full-Text Articles in Medical Sciences

Role Of The Distal Sara Promoters In Sara Expression In Staphylococcus Aureus, Ambrose L. Cheung, Adhar C. Manna Jul 2005

Role Of The Distal Sara Promoters In Sara Expression In Staphylococcus Aureus, Ambrose L. Cheung, Adhar C. Manna

Dartmouth Scholarship

The global regulatory locus sarA comprises a 375-bp open reading frame that is driven by three promoters, the proximal P1 and distal P3 and P2 promoters. We mutated the weaker P3 and P2 promoters to ascertain the effect of the change on SarA protein and target gene expression. Our results indicated that the solely active P1 promoter led to a lower SarA protein level, which has an effect on agr transcription and subsequently had corresponding effects on hla, sspA, and spa transcription, probably in both agr-independent and agr-dependent manners.


Effects Of Estradiol On Lipopolysaccharide And Pam3cys Stimulation Of Ccl20/Macrophage Inflammatory Protein 3 Alpha And Tumor Necrosis Factor Alpha Production By Uterine Epithelial Cells In Culture, Mardi A. Crane-Godreau, Charles R. Wira Jul 2005

Effects Of Estradiol On Lipopolysaccharide And Pam3cys Stimulation Of Ccl20/Macrophage Inflammatory Protein 3 Alpha And Tumor Necrosis Factor Alpha Production By Uterine Epithelial Cells In Culture, Mardi A. Crane-Godreau, Charles R. Wira

Dartmouth Scholarship

We have previously demonstrated that rat uterine epithelial cells (UEC) produce CCL20/macrophage inflammatory protein 3 alpha (MIP3alpha) and tumor necrosis factor alpha (TNF-alpha) in response to live and heat-killed Escherichia coli and to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and Pam3Cys. To determine whether estradiol (E2) modulates PAMP-induced CCL20/MIP3alpha and TNF-alpha secretion, primary cultures of rat UEC were incubated with E2 for 24 h and then treated with LPS or Pam3Cys or not treated for an additional 12 h. E2 inhibited the constitutive secretion of TNF-alpha and CCL20/MIP3alpha into culture media. Interestingly, E2 pretreatment enhanced CCL20/MIP3alpha secretion due to …


Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung Jul 2005

Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung

Dartmouth Scholarship

Chronic airway infection is a hallmark of cystic fibrosis (CF) and many CF patients are infected persistently by Staphylococcus aureus. Thymidine-dependent trimethoprim-sulfamethoxazole (SXT)-resistant S. aureus small-colony variants (SCVs), often in combination with isogenic normal S. aureus phenotypes, are highly prevalent and persistent in airway secretions of CF patients due to long-term SXT therapy (B. Kahl, M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E. Harms, R. A. Proctor, and G.


Environmental Factors In Autoimmunity: Assessment Of Immunotoxicity Of Phthalates In The Induction Of Lupus-Type Anti-Dna Antibodies, So-Yon Lim May 2005

Environmental Factors In Autoimmunity: Assessment Of Immunotoxicity Of Phthalates In The Induction Of Lupus-Type Anti-Dna Antibodies, So-Yon Lim

All-Inclusive List of Electronic Theses and Dissertations

Objectives: Little is known of the role of specific environmental factors in promoting autoimmune disorders such as systemic lupus erythematosus (SLE). The broad objective of this study was to address how exposure to phthalates, common environmental factors m foods, and biomedical devices could affect the immune functions of resistant and autoimmune-prone mice. Methods: The environmental chemical model used in this study is phthalates, which are widely used in various forms and readily occur during day-to-day human contacts. Groups of nonautoimmune-prone (BALB/c, DBA/2 and C57BL/6) and susceptible (NZB, NZB/W Fl) mice were immunized with phthalates ( ortho, meta and para) conjugated …


Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin Apr 2005

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …


Rat/Mgra, A Regulator Of Autolysis, Is A Regulator Of Virulence Genes In Staphylococcus Aureus, Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung Mar 2005

Rat/Mgra, A Regulator Of Autolysis, Is A Regulator Of Virulence Genes In Staphylococcus Aureus, Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung

Dartmouth Scholarship

We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of α-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and …


Peptide 15-Mers Of Defined Sequence That Substitute For Random Amino Acid Copolymers In Amelioration Of Experimental Autoimmune Encephalomyelitis, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Masha Fridkis-Hareli, Vijay K. Kuchroo, Jack L. Strominger Feb 2005

Peptide 15-Mers Of Defined Sequence That Substitute For Random Amino Acid Copolymers In Amelioration Of Experimental Autoimmune Encephalomyelitis, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Masha Fridkis-Hareli, Vijay K. Kuchroo, Jack L. Strominger

Jay Reddy Publications

Myelin basic protein (MBP) is a major candidate autoantigen in multiple sclerosis (MS). Its immunodominant epitope, MBP 85–99, forms a complex with human leukocyte antigen (HLA)-DR2 with which multiple sclerosis is genetically associated. Copolymer 1 (Copaxone), a random amino acid copolymer [poly (Y,E,A,K)n] as well as two modified synthetic copolymers [poly (F,Y,A,K)n and poly (V,W,A,K)n] also form complexes with HLA-DR2 (DRA DRB1*1501) and compete with MBP 85–99 for binding. Moreover, two high-affinity synthetic peptide 15-mers that could inhibit binding even more effectively were previously designed. Here, we show that further-modified peptide 15-mers inhibited even more strongly (in order J5 > J3 …


Replication And Encapsidation Of Papillomaviruses In Saccharomyces Cerevisiae, Peter C. Angeletti Jan 2005

Replication And Encapsidation Of Papillomaviruses In Saccharomyces Cerevisiae, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Improvements in methodologies to recapitulate and study particular biological functions of the

papillomavirus life cycle have led to great advances in our knowledge of these viruses. Described in

this chapter are techniques that allow low-copy and high-copy replication of full-length human

papillomavirus (HPV) genomes, as well as assembly of virus-like particles, in Saccharomyces

cerevisiae (yeast). This system has several distinct advantages that make it an attractive complement

to the well-established raft-culturing system. First, yeast are inexpensive, rapid, and simple to culture

in the lab. Second, they provide an ever-widening array of genetic tools to analyze HPV functions

—most recently notable, …


Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes Jan 2005

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …


Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes Jan 2005

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …


Association Between Coinfection Of Porphyromonas Gingivalis, Actinobacillus Actinomycetemcomitans And Treponema Denticola And Periodontal Tissue Destruction In Chronic Periodontitis, L. L. Chen, Y. M. Wu, J. Yan, W. L. Sun, Y. Z. Sun, David M. Ojcius Jan 2005

Association Between Coinfection Of Porphyromonas Gingivalis, Actinobacillus Actinomycetemcomitans And Treponema Denticola And Periodontal Tissue Destruction In Chronic Periodontitis, L. L. Chen, Y. M. Wu, J. Yan, W. L. Sun, Y. Z. Sun, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

No abstract provided.


Ccl20/Macrophage Inflammatory Protein 3Α And Tumor Necrosis Factor Alpha Production By Primary Uterine Epithelial Cells In Response To Treatment With Lipopolysaccharide Or Pam3cys, M. A. Crane-Godreau, C. R. Wira Jan 2005

Ccl20/Macrophage Inflammatory Protein 3Α And Tumor Necrosis Factor Alpha Production By Primary Uterine Epithelial Cells In Response To Treatment With Lipopolysaccharide Or Pam3cys, M. A. Crane-Godreau, C. R. Wira

Dartmouth Scholarship

Having previously shown that CCL20/macrophage inflammatory protein 3 and tumor necrosis factor alpha (TNF-alpha) are released by polarized primary rat uterine epithelial cells (UEC) in response to Escherichia coli but not to Lactobacillus rhamnosus , we sought to determine if epithelial cells are responsive to pathogen-associated molecular patterns (PAMP), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), and Pam 3 Cys, a bacterial lipoprotein analog. Epithelial cells were grown to confluence on Nunc cell culture inserts prior to apical treatment with PAMPs. In response to LPS, LTA, and Pam 3 Cys (EMC Microcollection GmbH, Tu ̈- bingen, Germany), CCL20 levels increased (4- …


Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important For Generation Of An Optimal Polymorphonuclear Response Against Toxoplasma Gondii Infection, Michelle N. Kelly, Jay K. Kolls, Kyle Happel, Joseph D. Schwartzman Jan 2005

Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important For Generation Of An Optimal Polymorphonuclear Response Against Toxoplasma Gondii Infection, Michelle N. Kelly, Jay K. Kolls, Kyle Happel, Joseph D. Schwartzman

Dartmouth Scholarship

We investigated the role of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity against Toxoplasma gondii. IL-17R−/− mice developed a normal adaptive immunity against the parasite. However, increased mortality in the knockout animals can be attributed to a defect in the migration of polymorphonuclear leukocytes to infected sites during early infection.


Role Of A Cytotoxic-T-Lymphocyte Epitope-Defined, Alternative Gag Open Reading Frame In The Pathogenesis Of A Murine Retrovirus-Induced Immunodeficiency Syndrome, Arti Gaur, William R. Green Nov 2004

Role Of A Cytotoxic-T-Lymphocyte Epitope-Defined, Alternative Gag Open Reading Frame In The Pathogenesis Of A Murine Retrovirus-Induced Immunodeficiency Syndrome, Arti Gaur, William R. Green

Dartmouth Scholarship

LP-BM5 murine leukemia virus-infected C57BL/6 mice develop profound immunodeficiency and B-cell lymphomas. The LP-BM5 complex contains a mixture of defective (BM5def) and replication-competent helper viruses among which BM5def is the primary causative agent of disease. The BM5def primary open reading frame (ORF1) encodes the single gag precursor protein (Pr60gag). Our lab has recently demonstrated that a novel immunodominant cytotoxic-T-lymphocyte (CTL) epitope (SYNTGRFPPL) is expressed from a +1-nucleotide translational open reading frame of BM5def during the course of normal retrovirus expression. The SYNTGRFPPL CTL epitope may be generated from either of two initiation methionines present, ORF2a or ORF2b, located …


Differential Expression Of Toll-Like Receptors 2 And 4 In Tissues Of The Human Female Reproductive Tract, Patricia A. Pioli, Eyal Amiel, Todd M. Schaefer, John E. Connolly, Charles R. Wira, Paul M. Guyre Oct 2004

Differential Expression Of Toll-Like Receptors 2 And 4 In Tissues Of The Human Female Reproductive Tract, Patricia A. Pioli, Eyal Amiel, Todd M. Schaefer, John E. Connolly, Charles R. Wira, Paul M. Guyre

Dartmouth Scholarship

Toll-like receptor (TLR) signal transduction is a central component of the innate immune response to pathogenic challenge. Although recent studies have begun to elucidate differences in acquired immunity in tissues of the human female reproductive tract, there is a relative paucity of work regarding innate defense mechanisms. We investigated TLR mRNA and protein expression in tissues of the human female reproductive tract. Constitutive mRNA expression of TLRs 1 to 6 was observed in fallopian tubes, uterine endometrium, cervix, and ectocervix. Furthermore, transcripts of the signaling adapter MyD88 and the accessory molecule CD14 were also detected in all tissues assayed. Quantitative …


T-Cell Responses To The M3 Immune Evasion Protein Of Murid Gammaherpesvirus 68 Are Partially Protective And Induced With Lytic Antigen Kinetics, Joshua J. Obar, Douglas C. Donovan, Sarah G. Crist, Ondine Silvia, James P. Stewart, Edward J. Usherwood Oct 2004

T-Cell Responses To The M3 Immune Evasion Protein Of Murid Gammaherpesvirus 68 Are Partially Protective And Induced With Lytic Antigen Kinetics, Joshua J. Obar, Douglas C. Donovan, Sarah G. Crist, Ondine Silvia, James P. Stewart, Edward J. Usherwood

Dartmouth Scholarship

DNA vaccination with the M3 gene, encoding an immune evasion molecule expressed during both the acute lytic and persistent phases of murid gammaherpesvirus 68 infection, yielded a significantly lower titer of virus in the lung than controls. The protection seen was dependent on T cells, and we mapped an epitope recognized by CD8 T cells. The immune response to this epitope follows the same kinetics as lytic cycle antigens, despite the fact that this gene is expressed in both lytic and persistent stages of infection. This has important implications for our understanding of T-cell responses to putative latency-associated gammaherpesvirus proteins …


A Vibrio Cholerae Classical Tcpa Amino Acid Sequence Induces Protective Antibody That Binds An Area Hypothesized To Be Important For Toxin-Coregulated Pilus Structure, Ronald K. Taylor, Thomas J. Kirn, Michael D. Meeks, Terri K. Wade, William F. Wade Oct 2004

A Vibrio Cholerae Classical Tcpa Amino Acid Sequence Induces Protective Antibody That Binds An Area Hypothesized To Be Important For Toxin-Coregulated Pilus Structure, Ronald K. Taylor, Thomas J. Kirn, Michael D. Meeks, Terri K. Wade, William F. Wade

Dartmouth Scholarship

Vibrio cholerae is a gram-negative bacterium that has been associated with cholera pandemics since the early 1800s. Whole-cell, killed, and live-attenuated oral cholera vaccines are in use. We and others have focused on the development of a subunit cholera vaccine that features standardized epitopes from various V. cholerae macromolecules that are known to induce protective antibody responses. TcpA protein is assembled into toxin-coregulated pilus (TCP), a type IVb pilus required for V. cholerae colonization, and thus is a strong candidate for a cholera subunit vaccine. Polypeptides (24 to 26 amino acids) in TcpA that can induce protective antibody responses have …


Il-2 Receptor Signaling Regulates Ets1 Translation In Human Natural Killer Cells, Eric M. Grund Sep 2004

Il-2 Receptor Signaling Regulates Ets1 Translation In Human Natural Killer Cells, Eric M. Grund

MUSC Theses and Dissertations

Natural Killer (NK) cells are critical for protection from cancer and infectious disease. The hypothesis that there is a molecular link between IL-2 receptor signaling and Ets1 was investigated. This hypothesis was based on the correlation between an NK-deficient phenotype generated by gene targeting of the Ets1 transcription factor, IL-2 receptor, IL-2 and IL-15, indicating that each of these proteins is required for the proper development and function of NK cells. The findings presented show that both IL-2 and IL-15 induce a post-transcriptional regulation of Ets1 in NK cells. Pharmacological and transient transfection analyses, using a method developed within to …


Cd4+ T Cells In The Pathogenesis Of Murine Ocular Toxoplasmosis, Fangli Lu, Shiguang Huang, Lloyd H. Kasper Sep 2004

Cd4+ T Cells In The Pathogenesis Of Murine Ocular Toxoplasmosis, Fangli Lu, Shiguang Huang, Lloyd H. Kasper

Dartmouth Scholarship

The role of CD4+ T cells in the pathogenesis of ocular toxoplasmosis was investigated in murine models utilizing inbred C57BL/6 mice deficient either in CD4+, CD8+, or B cells (μMT). Severe necrosis and inflammation with replicating parasites were observed in the eyes of control mice after primary ocular infection, and near-normal histology with few tachyzoites was observed in the eyes of mice immunized intraperitoneally with the avirulent ts-4 strain followed by intraocular challenge with the RH strain of Toxoplasma gondii. In contrast, mild inflammation without evidence of necrosis associated with increased parasite burdens were …


Durable Cytotoxic Immune Responses Against Gp120 Elicited By Recombinant Sv40 Vectors Encoding Hiv-1 Gp120 +/- Il-15., Hayley J Mckee, Patricia Y T'Sao, Maria Vera, Puri Fortes, David S Strayer Aug 2004

Durable Cytotoxic Immune Responses Against Gp120 Elicited By Recombinant Sv40 Vectors Encoding Hiv-1 Gp120 +/- Il-15., Hayley J Mckee, Patricia Y T'Sao, Maria Vera, Puri Fortes, David S Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: A vaccine that elicits durable, powerful anti-HIV immunity remains an elusive goal. In these studies we tested whether multiple treatments with viral vector-delivered HIV envelope antigen (gp120), with and without IL-15, could help to approach that goal. For this purpose, we used recombinant Tag-deleted SV40-derived vectors (rSV40s), since they do not elicit neutralizing antibody responses, and so can be given multiply without loss of transduction efficiency. METHODS: SV(gp120) carried the coding sequences for HIV-1NL4-3 Env, and SV(mIL-15) carried the cDNA for mouse IL-15. Singly, and in combination, these two vectors were given monthly to BALB/cJ mice. Cytotoxic immunity and …


The Major Subunit Of The Toxin-Coregulated Pilus Tcpa Induces Mucosal And Systemic Immunoglobulin A Immune Responses In Patients With Cholera Caused By Vibrio Cholerae O1 And O139, Muhammad Asaduzzaman, Edward T. Ryan, Manohar John, Long Hang, Ashraful I. Khan, A. S. G. Faruque, Ronald K. Taylor Aug 2004

The Major Subunit Of The Toxin-Coregulated Pilus Tcpa Induces Mucosal And Systemic Immunoglobulin A Immune Responses In Patients With Cholera Caused By Vibrio Cholerae O1 And O139, Muhammad Asaduzzaman, Edward T. Ryan, Manohar John, Long Hang, Ashraful I. Khan, A. S. G. Faruque, Ronald K. Taylor

Dartmouth Scholarship

Diarrhea caused by Vibrio cholerae is known to give long-lasting protection against subsequent life-threatening illness. The serum vibriocidal antibody response has been well studied and has been shown to correlate with protection. However, this systemic antibody response may be a surrogate marker for mucosal immune responses to key colonization factors of this organism, such as the toxin-coregulated pilus (TCP) and other factors. Information regarding immune responses to TCP, particularly mucosal immune responses, is lacking, particularly for patients infected with the El Tor biotype of V. cholerae O1 or V. cholerae O139 since highly purified TcpA from these strains has not …


Gitr Activation Induces An Opposite Effect On Alloreactive Cd4(+) And Cd8(+) T Cells In Graft-Versus-Host Disease., Stephanie J Muriglan, Teresa Ramirez-Montagut, Onder Alpdogan, Thomas W Van Huystee, Jeffrey M Eng, Vanessa M Hubbard, Adam A Kochman, Kartono H Tjoe, Carlo Riccardi, Pier Paolo Pandolfi, Shimon Sakaguchi, Alan N Houghton, Marcel R M Van Den Brink Jul 2004

Gitr Activation Induces An Opposite Effect On Alloreactive Cd4(+) And Cd8(+) T Cells In Graft-Versus-Host Disease., Stephanie J Muriglan, Teresa Ramirez-Montagut, Onder Alpdogan, Thomas W Van Huystee, Jeffrey M Eng, Vanessa M Hubbard, Adam A Kochman, Kartono H Tjoe, Carlo Riccardi, Pier Paolo Pandolfi, Shimon Sakaguchi, Alan N Houghton, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4(+) and CD8(+) T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8(+)CD25(-) T …


Activation Of The Phosphatidylinositol 3-Kinase/Akt Pathway Contributes To Survival Of Primary Epithelial Cells Infected With The Periodontal Pathogen Porphyromonas Gingivalis, Özlem Yilmaz, Thomas Jungas, Philippe Verbeke, David M. Ojcius Jul 2004

Activation Of The Phosphatidylinositol 3-Kinase/Akt Pathway Contributes To Survival Of Primary Epithelial Cells Infected With The Periodontal Pathogen Porphyromonas Gingivalis, Özlem Yilmaz, Thomas Jungas, Philippe Verbeke, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Porphyromonas gingivalis, an important periodontal pathogen, infects primary gingival epithelial cells (GECs). Despite the large number of bacteria that replicate inside the GECs, the host cell remains viable. We demonstrate that P. gingivalis triggers rapid and reversible surface phosphatidylserine exposure through a mechanism requiring caspase activation. However, after 1 day of infection, the bacteria no longer induce phosphatidylserine externalization and instead protect infected cells against apoptosis. Infection exerts its effect at the level of mitochondria, as P. gingivalis also blocks depolarization of the mitochondrial transmembrane potential and cytochrome c release. Interestingly, protein kinase B/Akt is phosphorylated during infection, which can …


Synthetic Fragments Of Vibrio Cholerae O1 Inaba O-Specific Polysaccharide Bound To A Protein Carrier Are Immunogenic In Mice But Do Not Induce Protective Antibodies, Michael D. Meeks, Rina Saksena, Xingquan Ma, Terri K. Wade, Ronald K. Taylor, Pavol Kováč, William F. Wade Jul 2004

Synthetic Fragments Of Vibrio Cholerae O1 Inaba O-Specific Polysaccharide Bound To A Protein Carrier Are Immunogenic In Mice But Do Not Induce Protective Antibodies, Michael D. Meeks, Rina Saksena, Xingquan Ma, Terri K. Wade, Ronald K. Taylor, Pavol Kováč, William F. Wade

Dartmouth Scholarship

Development of Vibrio cholerae lipopolysaccharide (LPS) as a cholera vaccine immunogen is justified by the correlation of vibriocidal anti-LPS response with immunity. Two V. cholerae O1 LPS serotypes, Inaba and Ogawa, are associated with endemic and pandemic cholera. Both serotypes induce protective antibody following infection or vaccination. Structurally, the LPSs that define the serotypes are identical except for the terminal perosamine moiety, which has a methoxyl group at position 2 in Ogawa but a hydroxyl group in Inaba. The terminal sugar of the Ogawa LPS is a protective B-cell epitope. We chemically synthesized the terminal hexasaccharides of V. cholerae serotype …


Combined Tlr And Cd40 Triggering Induces Potent Cd8+ T Cell Expansion With Variable Dependence On Type I Ifn, Cory L. Ahonen, Christie L. Doxsee, Sean M. M. Mcgurran, Tony R. Riter, William F. Wade, Richard J. Barth, John P. Vasilakos, Randolph J. Noelle, Ross M. Kedl Mar 2004

Combined Tlr And Cd40 Triggering Induces Potent Cd8+ T Cell Expansion With Variable Dependence On Type I Ifn, Cory L. Ahonen, Christie L. Doxsee, Sean M. M. Mcgurran, Tony R. Riter, William F. Wade, Richard J. Barth, John P. Vasilakos, Randolph J. Noelle, Ross M. Kedl

Dartmouth Scholarship

Toll-like receptors are important in the activation of innate immunity, and CD40 is a molecule critical for many T and B cell responses. Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10–20-fold greater than the use of either agonist alone. Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)γ production and an enhanced secondary response to antigenic challenge. Agonists for TLRs 2/6, 3, 4, and 9 also synergized with …


Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper Mar 2004

Immune Responses Of Different Mouse Strains After Challenge With Equivalent Lethal Doses Of Toxoplasma Gondii, Y. H. Lee, L. H. Kasper

Dartmouth Scholarship

Most immunological studies that utilize different strains of inbred mice following T. gondii infection fail to compensate for differences in host susceptibility to the size of the parasite innoculum. To address this concern, susceptible C57BL/6 and resistant CBA/J mice were orally infected with either an equivalent 50 % lethal dose (LD50) of brain cysts of the 76K strain of T. gondii (15 cysts in C57BL/6, 400 cysts in CBA/J) or the same dose of parasites in each mouse strain. C57BL/6 mice receiving 400 cysts (LD50 of CBA/J mice) died post infection, whereas CBA/J mice that received 15 …


Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu Feb 2004

Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu

Nebraska Center for Virology: Faculty Publications

Rigorous phylogenetic analyses were used to compare the nucleotide sequences of feline immunodeficiency virus strains isolated from Texas and throughout the world. The envelope V3-V4 sequences and capsid gene of the Texas isolates formed a cluster between subtypes B and E. Statistical comparisons with other published sequences confirmed that the Texas group is a unique cluster, possibly a new subtype, arising from subtype B.

Feline immunodeficiency virus (FIV) was initially isolated in 1987 from a cat in California with severe immunodeficiency and has been recognized as a common worldwide feline pathogen (11, 14, 19, 20, 33). FIV-infected cats exhibit a …


Cd46-Mediated Transduction Of A Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy, Zenaido T. Camacho, Mallory A. Turner, Michael A. Barry, Eric A. Weaver Jan 2004

Cd46-Mediated Transduction Of A Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy, Zenaido T. Camacho, Mallory A. Turner, Michael A. Barry, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The …


Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu Jan 2004

Phylogenetic Analyses Of Texas Isolates Indicate An Evolving Subtype Of The Clade B Feline Immunodeficiency Viruses, Eric A. Weaver, Ellen W. Collisson, Margaret Slater, Guan Zhu

Nebraska Center for Virology: Faculty Publications

Rigorous phylogenetic analyses were used to compare the nucleotide sequences of feline immunodeficiency virus strains isolated from Texas and throughout the world. The envelope V3-V4 sequences and capsid gene of the Texas isolates formed a cluster between subtypes B and E. Statistical comparisons with other published sequences confirmed that the Texas group is a unique cluster, possibly a new subtype, arising from subtype B.


Amelioration Of Proteolipid Protein 139–151-Induced Encephalomyelitis In Sjl Mice By Modified Amino Acid Copolymers And Their Mechanisms, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Eric Sheu, Masha Fridkis-Hareli, Hiroyuki Nishimura, Celia F. Brosnan, Laura Santambrogio, Vijay K. Kuchroo, Jack L. Strominger Jan 2004

Amelioration Of Proteolipid Protein 139–151-Induced Encephalomyelitis In Sjl Mice By Modified Amino Acid Copolymers And Their Mechanisms, Joel N.H. Stern, Zsolt Illés, Jay Reddy, Derin B. Keskin, Eric Sheu, Masha Fridkis-Hareli, Hiroyuki Nishimura, Celia F. Brosnan, Laura Santambrogio, Vijay K. Kuchroo, Jack L. Strominger

Jay Reddy Publications

Copolymer 1 [Cop1, glatiramer acetate, Copaxone, poly(Y,E,A,K)n] is widely used in the treatment of relapsing/remitting multiple sclerosis in which it reduces the frequency of relapses by ≈30%. In the present study, copolymers with modified amino acid compositions (based on the binding motif of myelin basic protein 85–99 to HLA-DR2) have been developed with the aim of suppressing multiple sclerosis more effectively. The enhanced efficacy of these copolymers in experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with proteolipid protein 139–151 was demonstrated by using three protocols: (i) simultaneous administration of autoantigen and copolymer (termed prevention), (ii) …