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Full-Text Articles in Medicine and Health Sciences
Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman
Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman
Dartmouth Scholarship
The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 …
Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk
Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk
Dartmouth Scholarship
Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4(+) T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, …
Mcl1 Enhances The Survival Of Cd8+ Memory T Cells After Viral Infection, Jingang Gui, Zhuting Hu, Ching-Yi Tsai, Tian Ma, Yan Song, Amanda Morales, Li-Hao Huang, Ethan Dmitrovsky, Ruth Craig, Edward Usherwood
Mcl1 Enhances The Survival Of Cd8+ Memory T Cells After Viral Infection, Jingang Gui, Zhuting Hu, Ching-Yi Tsai, Tian Ma, Yan Song, Amanda Morales, Li-Hao Huang, Ethan Dmitrovsky, Ruth Craig, Edward Usherwood
Dartmouth Scholarship
Viral infection results in the generation of massive numbers of activated effector CD8+ T cells that recognize viral components. Most of these are short-lived effector T cells (SLECs) that die after clearance of the virus. However, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (MPECs), which ultimately develop into memory cells. These can participate in a recall response upon reexposure to antigen even at protracted times postinfection. Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulation, and mice expressing human MCL1 as a transgene exhibited a skewing …
Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan
Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan
Dartmouth Scholarship
The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …
Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib
Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib
Dartmouth Scholarship
Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). …
The Differential Interferon Responses Of Two Strains Of Stat1-Deficient Mice Do Not Alter Susceptibility To Hsv-1 And Vsv In Vivo, Sarah Katzenell, Yufei Chen, Zachary M. Parker, David A. Leib
The Differential Interferon Responses Of Two Strains Of Stat1-Deficient Mice Do Not Alter Susceptibility To Hsv-1 And Vsv In Vivo, Sarah Katzenell, Yufei Chen, Zachary M. Parker, David A. Leib
Dartmouth Scholarship
Stat1 is a pivotal transcription factor for generation of the interferon (IFN)-dependent antiviral response. Two Stat1 knockout mouse lines have been previously generated, one deleted the N-terminal domain (ΔNTD) and one in the DNA-binding domain (ΔDBD). These widely-used strains are assumed interchangeable, and both are highly susceptible to various pathogens. In this study, primary cells derived from ΔNTD mice were shown to be significantly more responsive to IFN, and established an antiviral state with greater efficiency than cells derived from ΔDBD mice, following infection with vesicular stomatitis virus and herpes simplex virus type-1. Also, while mice from both strains succumbed …
Importance Of Bacillithiol In The Oxidative Stress Response Of Staphylococcus Aureus, Ana C. Posada, Stacey L. Kolar, Renata G. Dusi, Patrica Francois
Importance Of Bacillithiol In The Oxidative Stress Response Of Staphylococcus Aureus, Ana C. Posada, Stacey L. Kolar, Renata G. Dusi, Patrica Francois
Dartmouth Scholarship
In Staphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed mutants with the deletion of bshA (sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, and fosB (sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains, including clinical isolates. Mutation of fosB or bshA caused a 16- to 60-fold reduction in fosfomycin resistance in these S. aureus strains. High-pressure liquid chromatography analysis, which …
The Toxoplasma Gondii Cyst Wall Protein Cst1 Is Critical For Cyst Wall Integrity And Promotes Bradyzoite Persistence, Tadakimi Tomita, David J. Bzik, Yan Fen Ma, Barbara A. Fox
The Toxoplasma Gondii Cyst Wall Protein Cst1 Is Critical For Cyst Wall Integrity And Promotes Bradyzoite Persistence, Tadakimi Tomita, David J. Bzik, Yan Fen Ma, Barbara A. Fox
Dartmouth Scholarship
Toxoplasma gondii infects up to one third of the world's population. A key to the success of T. gondii as a parasite is its ability to persist for the life of its host as bradyzoites within tissue cysts. The glycosylated cyst wall is the key structural feature that facilitates persistence and oral transmission of this parasite. Because most of the antibodies and reagents that recognize the cyst wall recognize carbohydrates, identification of the components of the cyst wall has been technically challenging. We have identified CST1 (TGME49_064660) as a 250 kDa SRS (SAG1 related sequence) domain protein with a large …
Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky
Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky
Dartmouth Scholarship
Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …
Flagellar Motility Is A Key Determinant Of The Magnitude Of The Inflammasome Response To Pseudomonas Aeruginosa, Yash R. Patankar, Rustin R. Lovewell, Matthew E. Poynter, Jeevan Jyot, Barbara I. Kazmierczak, Brent Berwin
Flagellar Motility Is A Key Determinant Of The Magnitude Of The Inflammasome Response To Pseudomonas Aeruginosa, Yash R. Patankar, Rustin R. Lovewell, Matthew E. Poynter, Jeevan Jyot, Barbara I. Kazmierczak, Brent Berwin
Dartmouth Scholarship
We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report …
Step-Wise Loss Of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion, Rustin R. Lovewell, Ryan M. Collins, Julie L. Acker, George A. O'Toole, Matthew J. Wargo, Brent Berwin, Craig R. Roy
Step-Wise Loss Of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion, Rustin R. Lovewell, Ryan M. Collins, Julie L. Acker, George A. O'Toole, Matthew J. Wargo, Brent Berwin, Craig R. Roy
Dartmouth Scholarship
Phagocytosis of bacteria by innate immune cells is a primary method of bacterial clearance during infection. However, the mechanisms by which the host cell recognizes bacteria and consequentially initiates phagocytosis are largely unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated that bacterial flagella and flagellar motility play an important role in colonization of the host and, importantly, that loss of flagellar motility enables phagocytic evasion. Here we use molecular, cellular, and genetic methods to provide the first formal evidence that phagocytic cells recognize bacterial motility rather than flagella and initiate phagocytosis in response to this motility. We demonstrate …
A Retinoic Acid–Dependent Checkpoint In The Development Of Cd4+ T Cell–Mediated Immunity, Karina Pino-Lagos, Yanxia Guo, Chrysothemis Brown, Matthew P. Alexander, Raúl Elgueta, Kathryn A. Bennett, Victor De Vries, Elizabeth Nowak, Rune Blomhoff, Shanthini Sockanathan, Roshantha A. Chandraratna, Ethan Dmitrovsky, Randolph J. Noelle
A Retinoic Acid–Dependent Checkpoint In The Development Of Cd4+ T Cell–Mediated Immunity, Karina Pino-Lagos, Yanxia Guo, Chrysothemis Brown, Matthew P. Alexander, Raúl Elgueta, Kathryn A. Bennett, Victor De Vries, Elizabeth Nowak, Rune Blomhoff, Shanthini Sockanathan, Roshantha A. Chandraratna, Ethan Dmitrovsky, Randolph J. Noelle
Dartmouth Scholarship
It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4+ T cell effector function, migration, and polarity. These findings provide a new perspective of the role of …
Avirulent Uracil Auxotrophs Based On Disruption Of Orotidine-5′-Monophosphate Decarboxylase Elicit Protective Immunity To Toxoplasma Gondii, Barbara A. Fox, David J. Bzik
Avirulent Uracil Auxotrophs Based On Disruption Of Orotidine-5′-Monophosphate Decarboxylase Elicit Protective Immunity To Toxoplasma Gondii, Barbara A. Fox, David J. Bzik
Dartmouth Scholarship
The orotidine-5'-monophosphate decarboxylase (OMPDC) gene, encoding the final enzyme of the de novo pyrimidine biosynthesis pathway, was deleted using Toxoplasma gondii KU80 knockouts to develop an avirulent nonreverting pyrimidine auxotroph strain. Additionally, to functionally address the role of the pyrimidine salvage pathway, the uridine phosphorylase (UP) salvage activity was knocked out and a double knockout of UP and OMPDC was also constructed. The nonreverting DeltaOMPDC, DeltaUP, and DeltaOMPDC DeltaUP knockout strains were evaluated for pyrimidine auxotrophy, for attenuation of virulence, and for their ability to elicit potent immunity to reinfection. The DeltaUP knockout strain was replication competent and virulent. In …
Cd4+ T Cell Regulation Of Cd25 Expression Controls Development Of Short-Lived Effector Cd8+ T Cells In Primary And Secondary Responses, Joshua J. Obar, Michael J. Molloy, Evan R. Jellison, Thomas A. Stoklasek, Weijun Zhang, Edward J. Usherwood, Leo Lefrançois
Cd4+ T Cell Regulation Of Cd25 Expression Controls Development Of Short-Lived Effector Cd8+ T Cells In Primary And Secondary Responses, Joshua J. Obar, Michael J. Molloy, Evan R. Jellison, Thomas A. Stoklasek, Weijun Zhang, Edward J. Usherwood, Leo Lefrançois
Dartmouth Scholarship
Both CD4(+) T cell help and IL-2 have been postulated to "program" activated CD8(+) T cells for memory cell development. However, the linkage between these two signals has not been well elucidated. Here we have studied effector and memory CD8(+) T cell differentiation following infection with three pathogens (Listeria monocytogenes, vesicular stomatitis virus, and vaccinia virus) in the absence of both CD4(+) T cells and IL-2 signaling. We found that expression of CD25 on antigen-specific CD8(+) T cells peaked 3-4 days after initial priming and was dependent on CD4(+) T cell help, likely through a CD28:CD80/86 mediated pathway. CD4(+) T …
Sarz Promotes The Expression Of Virulence Factors And Represses Biofilm Formation By Modulating Sara And Agr In Staphylococcus Aureus, Sandeep Tamber, Ambrose L. Cheung
Sarz Promotes The Expression Of Virulence Factors And Represses Biofilm Formation By Modulating Sara And Agr In Staphylococcus Aureus, Sandeep Tamber, Ambrose L. Cheung
Dartmouth Scholarship
Staphylococcus aureus is a remarkably adaptable organism capable of multiple modes of growth in the human host, as a part of the normal flora, as a pathogen, or as a biofilm. Many of the regulatory pathways governing these modes of growth are centered on the activities of two regulatory molecules, the DNA binding protein SarA and the regulatory RNAIII effector molecule of the agr system. Here, we describe the modulation of these regulators and their downstream target genes by SarZ, a member of the SarA/MarR family of transcriptional regulators. Transcriptional and phenotypic analyses of a sarZ mutant demonstrated that the …
Characterization Of Two Outer Membrane Proteins, Flgo And Flgp, That Influence Vibrio Cholerae Motility, Raquel M. Martinez, Madushini N. Dharmasena, Thomas J. Kirn, Ronald K. Taylor
Characterization Of Two Outer Membrane Proteins, Flgo And Flgp, That Influence Vibrio Cholerae Motility, Raquel M. Martinez, Madushini N. Dharmasena, Thomas J. Kirn, Ronald K. Taylor
Dartmouth Scholarship
Vibrio cholerae is highly motile by the action of a single polar flagellum. The loss of motility reduces the infectivity of V. cholerae, demonstrating that motility is an important virulence factor. FlrC is the sigma-54-dependent positive regulator of flagellar genes. Recently, the genes VC2206 (flgP) and VC2207 (flgO) were identified as being regulated by FlrC via a microarray analysis of an flrC mutant (D. C. Morris, F. Peng, J. R. Barker, and K. E. Klose, J. Bacteriol. 190:231-239, 2008). FlgP is reported to be an outer membrane lipoprotein required for motility that functions as a colonization factor. The study reported …
Kinetics And Phenotype Of Vaccine-Induced Cd8+ T-Cell Responses To Toxoplasma Gondii, Kimberly A. Jordan, Emma H. Wilson, Elia D. Tait, Barbara A. Fox, David S. Roos, David J. Bzik
Kinetics And Phenotype Of Vaccine-Induced Cd8+ T-Cell Responses To Toxoplasma Gondii, Kimberly A. Jordan, Emma H. Wilson, Elia D. Tait, Barbara A. Fox, David S. Roos, David J. Bzik
Dartmouth Scholarship
Multiple studies have established that the ability of CD8+ T cells to act as cytolytic effectors and produce gamma interferon is important in mediating resistance to the intracellular parasite Toxoplasma gondii. To better understand the generation of the antigen-specific CD8+ T-cell responses induced by T. gondii, mice were immunized with replication-deficient parasites that express the model antigen ovalbumin (OVA). Class I tetramers specific for SIINFEKL were used to track the OVA-specific endogenous CD8+ T cells. The peak CD8+ T-cell response was found at day 10 postimmunization, after which the frequency and numbers of antigen-specific cells …
Mgra Represses Biofilm Formation In Staphylococcus Aureus, Maria P. Trotonda, Sandeep Tamber, Guido Memmi, Ambrose L. Cheung
Mgra Represses Biofilm Formation In Staphylococcus Aureus, Maria P. Trotonda, Sandeep Tamber, Guido Memmi, Ambrose L. Cheung
Dartmouth Scholarship
MgrA is a pleiotropic regulator that controls autolysis, virulence, and efflux pump activity in Staphylococcus aureus. We recently found that mgrA mutants of strains RN6390, SH1000, and MW2 also displayed enhanced biofilm formation compared with their respective parents. The biofilms formed by mgrA mutants of RN6390 and MW2 are independent of sigB and ica loci, two genetic elements that have been previously associated with biofilm formation in S. aureus. Biofilms formed by mgrA mutants are dependent on the expression of surface proteins mediated by the sortase gene srtA. Extracellular DNA was also a crucial component of the early biofilm of …
All-Trans Retinoic Acid Mediates Enhanced T Reg Cell Growth, Differentiation, And Gut Homing In The Face Of High Levels Of Co-Stimulation, Micah J. Benson, Karina Pino-Lagos, Mario Rosemblatt, Randolph J. Noelle
All-Trans Retinoic Acid Mediates Enhanced T Reg Cell Growth, Differentiation, And Gut Homing In The Face Of High Levels Of Co-Stimulation, Micah J. Benson, Karina Pino-Lagos, Mario Rosemblatt, Randolph J. Noelle
Dartmouth Scholarship
We demonstrate that all-trans retinoic acid (RA) induces FoxP3(+) adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (alpha 4 beta 7(+) CC chemokine receptor 9(+)) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-beta1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4(+) T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence …
Gammaherpesvirus Persistence Alters Key Cd8 T-Cell Memory Characteristics And Enhances Antiviral Protection, Joshua J. Obar, Shinichiro Fuse, Erica K. Leung, Sarah C. Bellfy, Edward J. Usherwood
Gammaherpesvirus Persistence Alters Key Cd8 T-Cell Memory Characteristics And Enhances Antiviral Protection, Joshua J. Obar, Shinichiro Fuse, Erica K. Leung, Sarah C. Bellfy, Edward J. Usherwood
Dartmouth Scholarship
In herpesvirus infections, the virus persists for life but is contained through T-cell-mediated immune surveillance. How this immune surveillance operates is poorly understood. Recent studies of other persistent infections have indicated that virus persistence is associated with functional deficits in the CD8(+) T-cell response. To test whether this is the case in a herpesvirus infection, we used a mutant murine gammaherpesvirus that is defective in its ability to persist in the host. By comparing the immune response to this virus with a revertant virus that can persist, we were able to dissect the changes in the antiviral CD8(+) T-cell response …
A Genetic Lesion That Arrests Plasma Cell Homing To The Bone Marrow, Loren D. Erickson, Ling-Li Lin, Biyan Duan, Laurence Morel, Randolph J. Noelle
A Genetic Lesion That Arrests Plasma Cell Homing To The Bone Marrow, Loren D. Erickson, Ling-Li Lin, Biyan Duan, Laurence Morel, Randolph J. Noelle
Dartmouth Scholarship
The coordinated regulation of chemokine responsiveness plays a critical role in the development of humoral immunity. After antigen challenge and B cell activation, the emerging plasma cells (PCs) undergo CXCL12-induced chemotaxis to the bone marrow, where they produce Ab and persist. Here we show that PCs, but not B cells or T cells from lupus-prone NZM mice, are deficient in CXCL12-induced migration. PC unresponsiveness to CXCL12 results in a marked accumulation of PCs in the spleen of mice, and a concordant decrease in bone marrow PCs. Unlike normal mice, in NZM mice, a majority of the splenic PCs are long-lived. …
The Cd154/Cd40 Interaction Required For Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated By Upregulation Of The Cd80/Cd86 Costimulatory Molecules, Kathy A. Green, W. James Cook, Arlene H. Sharpe, William R. Green
The Cd154/Cd40 Interaction Required For Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated By Upregulation Of The Cd80/Cd86 Costimulatory Molecules, Kathy A. Green, W. James Cook, Arlene H. Sharpe, William R. Green
Dartmouth Scholarship
C57BL/6 (B6) mice infected with LP-BM5 retroviruses develop disease, including an immunodeficiency similar to AIDS. This disease, murine AIDS (MAIDS), is inhibited by in vivo anti-CD154 monoclonal antibody treatment. The similar levels of insusceptibility of CD40−/− and CD154−/− B6 mice indicate that CD154/CD40 molecular interactions are required for MAIDS. CD4+ T and B cells, respectively, provide the CD154 and CD40 expression needed for MAIDS induction. Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86−/− B6 mice develop MAIDS after LP-BM5 infection.
Ups And Downs Of Mucosal Cellular Immunity Against Protozoan Parasites, Lloyd H. Kasper, Dominique Buzoni-Gatel
Ups And Downs Of Mucosal Cellular Immunity Against Protozoan Parasites, Lloyd H. Kasper, Dominique Buzoni-Gatel
Dartmouth Scholarship
No abstract provided.
Camp Antagonizes Interleukin 2-Promoted T-Cell Cycle Progression At A Discrete Point In Early G1., Kirk W. Johnson, Bruce H. Davis, Kendall A. Smith
Camp Antagonizes Interleukin 2-Promoted T-Cell Cycle Progression At A Discrete Point In Early G1., Kirk W. Johnson, Bruce H. Davis, Kendall A. Smith
Dartmouth Scholarship
T lymphocytes are stimulated to proliferate in an autocrine/paracrine manner by the lymphokine interleukin 2 (IL-2). In seeking further insight into the mechanisms by which IL-2 induces progression of T cells through the G1 phase of the cell cycle, studies were performed with agents that increase cellular adenosine 3',5'-cyclic monophosphate (cAMP), a well-known inhibitor of lymphocyte growth. The addition of dibutyryl-cAMP, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine to an IL-2-dependent murine T-cell line evoked a dose-related suppression of S-phase transition without affecting cellular viability. Moreover, elevation of cAMP levels led to an accumulation of uniformly small cells, suggesting an arrest in …
Rat Dendritic Cells Function As Accessory Cells And Control The Production Of A Soluble Factor Required For Mitogenic Responses Of T Lymphocytes., Wolfgang E. Klinkert, Jon H. Labadie, James P. O'Brien, Carl F. Beyer, William E. Bowers
Rat Dendritic Cells Function As Accessory Cells And Control The Production Of A Soluble Factor Required For Mitogenic Responses Of T Lymphocytes., Wolfgang E. Klinkert, Jon H. Labadie, James P. O'Brien, Carl F. Beyer, William E. Bowers
Dartmouth Scholarship
Transformation of T lymphocytes, induced by treatment with periodate or with neuraminidase plus galactose oxidase, requires the participation of accessory cells. Procedures were developed for the fractionation of rat lymph node cells, by which most of the lymphocytes can be recovered as a major population of cells that do not respond to mitogenic stimulation unless accessory cells from a separated minor population are added. Further purification led to a 1000-fold overall increase in accessory activity per cell, with a 50-70% yield. The purest preparations were virtually free of macrophages and contained more than 90% typical dendritic cells. Maximum responses occurred …