Medicine and Health Sciences Commons^™

Comparative Genetic Analysis Of Genomic Dna Sequences Of Two Human Isolates Of Tanapox Virus, Steven H. Nazarian, John W. Barrett, A. Michael Frace, Melissa Olsen-Rasmussen, Marina Khristova, Mae Shaban, Sarah Neering, Yu Li, Inger K. Damon, Joseph J. Esposito, Karim Essani, Grant Mcfadden

United States Public Health Resources

Members of the genus Yatapoxvirus, which include Tanapox virus (TPV) and Yaba monkey tumor virus, infect primates including humans. Two strains of TPV isolated 50 years apart from patients infected from the equatorial region of Africa have been sequenced. The original isolate from a human case in the Tana River Valley, Kenya, in 1957 (TPV-Kenya) and an isolate from an infected traveler in the Republic of Congo in 2004 (TPV-RoC). Although isolated 50 years apart the genomes were highly conserved. The genomes differed at only 35 of 144,565 nucleotide positions (99.98% identical). We predict that TPV-RoC encodes 155 …

Social Capital And Rates Of Gonorrhea And Syphilis In The United States: Spatial Regression Analyses Of State-Level Associations, Salaam Semaan, Maya Sternberg, Akbar Zaidi, Sevgi O. Aral

United States Public Health Resources

We conducted spatial regression analysis to account for spatial clustering of sexually transmitted diseases (STDs) and to examine the state-level association between social capital (using Putnam’s public use data set) and rates of gonorrhea and syphilis. We conducted the analysis for the 48 contiguous states of the United States for 1990, 1995, and 2000 and controlled for the effects of regional variation in STD rates, and for state variation in poverty, income inequality, racial composition, and percentage aged 15–34 years. We compared the results of the spatial regression analysis with those of ordinary least squares (OLS) regression. Controlling for all …

Michigan Bovine Tuberculosis Eradication Project: 2007 Activities Report

Michigan Bovine Tuberculosis Bibliography and Database

Bovine tuberculosis (TB) is an infectious disease that is close to being eradicated in the United States, but still poses a significant risk to domestic livestock, wildlife, companion animals, and humans throughout the world. The Michigan Bovine TB Eradication Project involves a multi-agency team of experts from the Michigan departments of Agriculture, Natural Resources and Community Health, Michigan State University, and the US Department of Agriculture.

N-Acetylaspartate In The Cns: From Neurodiagnostics To Neurobiology, John R. Moffett, Brian Ross, Peethambaran Arun, Chikkathur N. Madhavarao, Aryan M. A. Namboodiri

Uniformed Services University of the Health Sciences

The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous systemspecific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal central nervous system (CNS) development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid …

Aids-Associated Viral Oncogenesis: Overview, Charles Wood

Nebraska Center for Virology: Faculty Publications

It has been 25 years since the acquired immunodeficiency syndrome (AIDS) was first described and over 23 years since the human immunodeficiency virus (HIV) associated with the disease was first discovered. In spite of the tremendous progress that was made in understanding both the disease and the virus, there are still millions of people infected, died, or living with the disease. As for the year 2005 alone, the Joint United Nations Programme on HIV/AIDS (http://www.UNAIDS.org) estimates that there are about 40 million people living with HIV/AIDS globally, and approximately 3 million people died from AIDS in the year. Globally, it …

Modulation Of Retroviral Restriction And Proteasome Inhibitor-Resistant Turnover By Changes In The Trim5Α B-Box 2 Domain, Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5α. We modeled the structure of the B-box 2 domain of TRIM5α based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5αhu or rhesus monkey TRIM5α_rh. However, alteration of arginine 119 of TRIM5α_hu or the corresponding arginine 121 of TRIM5α_rh diminished the abilities of …

The Meaning Of Good Parent–Child Relationships For Mexican American Adolescents, Lisa J. Crockett, Jill Brown, Stephen Russell, Yuh-Ling Shen

Department of Psychology: Faculty Publications

Perceptions of good parent–adolescent relationships were explored among 19 Mexican American high school students aged 14–17 who participated in focus group interviews on what it means for Mexican American teenagers to have good relationships with parents. Using a grounded theory approach, five general themes emerged in the responses, corresponding to open communication, instrumental and emotional support, indirect expressions of caring, parental control, and valued relationship qualities. Both genders described distinct relationships with mothers and fathers. Relationships with mothers were closer and more open than relationships with fathers, and mothers were seen as being more affectionate, lenient, and emotionally supportive, whereas …

Multilevel Models For The Experimental Psychologist: Foundations And Illustrative Examples, Lesa Hoffman, Michael J. Rovine

Department of Psychology: Faculty Publications

Although common in the educational and developmental areas, multilevel models are not often utilized in the analysis of data from experimental designs. This article illustrates how multilevel models can be useful with two examples from experimental designs with repeated measurements not involving time. One example demonstrates how to properly examine independent variables for experimental stimuli or individuals that are categorical, continuous, or semicontinuous in the presence of missing data. The second example demonstrates how response times and error rates can be modeled simultaneously within a multivariate model in order to examine speed–accuracy trade-offs at the experimental-condition and individual levels, as …

Population Inference With Mortality And Attrition In Longitudinal Studies On Aging: A Two-Stage Multiple Imputation Method, Ofer Harel, Scott M. Hofer, Lesa Hoffman, Nancy L. Pedersen

Department of Psychology: Faculty Publications

First paragraph:

Although there are numerous challenges for the investigation of aging-related changes in older adults, statistical analysis with incomplete data and the conceptualization of population processes related to mortality is one of the most difficult. Selective attrition and mortality selection within longitudinal studies on aging are intrinsically related to many aging-related changes and must be carefully considered in the analysis and interpretation of results (e.g., Baltes, 1968; Hofer & Sliwinski, 2006; Schaie, Labouvie, & Barrett, 1973). A key distinction is made between attrition (i.e., selective dropout) and mortality selection (i.e., selective survival) in that attrition affects characteristics of the …

Structure And Function Of A Chlorella Virus Encoded Glycosyltransferase, Ying Zhang, Ye Xiang, James L. Van Etten, Michael G. Rossmann

James Van Etten Publications

Paramecium bursaria chlorella virus-1 encodes at least 5 putative glycosyltransferases that are probably involved in the synthesis of the glycan components of the viral major capsid protein. The 1.6 Å crystal structure of one of these glycosyltransferases (A64R) has a mixed α/β fold containing a central, six-stranded β-sheet flanked by α-helices. Crystal structures of A64R, complexed with UDP, CMP, or GDP, established that only UDP bound to A64R in the presence of Mn2+, consistent with its high structural similarity to glycosyltransferases which utilize UDP as the sugar carrier. The structure of the complex of A64R, UDP-glucose, and Mn2+ showed that …

Sequence And Annotation Of The 288-Kb Atcv-1 Virus That Infects An Endosymbiotic Chlorella Strain Of The Heliozoon Acanthocystis Turfacea, Lisa A. Fitzgerald, Michael V. Graves, Xiao Li, James Hartigan, Artur J.P. Pfitzner, Ella Hoffart, James L. Van Etten

James Van Etten Publications

Acanthocystis turfacea chlorella virus (ATCV-1), a prospective member of the family Phycodnaviridae, genus Chlorovirus, infects a unicellular, eukaryotic, chlorella-like green alga, Chlorella SAG 3.83, that is a symbiont in the heliozoon A. turfacea. The 288,047-bp ATCV-1 genome is the first virus to be sequenced that infects Chlorella SAG 3.83. ATCV-1 contains 329 putative protein-encoding and 11 tRNA-encoding genes. The protein-encoding genes are almost evenly distributed on both strands and intergenic space is minimal. Thirty-four percent of the viral gene products resemble entries in the public databases, including some that are unexpected for a virus. For example, these …

Chlorella Viruses Contain Genes Encoding A Complete Polyamine Biosynthetic Pathway, Sascha Baumann, Adrienne Sander, James Gurnon, Giane M. Yanai-Balser, James L. Van Etten, Markus Piotrowski

James Van Etten Publications

Two genes encoding the putative polyamine biosynthetic enzymes agmatine iminohydrolase (AIH) and N-carbamoylputrescine amidohydrolase (CPA) were cloned from the chloroviruses PBCV-1, NY-2A and MT325. They were expressed in Escherichia coli to form C-terminal (His)6-tagged proteins and the recombinant proteins were purified by Ni2+- binding affinity chromatography. The biochemical properties of the two enzymes are similar to AIH and CPA enzymes from Arabidopsis thaliana and Pseudomonas aeruginosa. Together with the previously known virus genes encoding ornithine/arginine decarboxlyase (ODC/ADC) and homospermidine synthase, the chloroviruses have genes that encode a complete set of functional enzymes that synthesize the rare polyamine homospermidine from arginine …

Research Strategies To Reduce Bovine Tuberculosis Transmission From Wildlife To Cattle, Are R. Brentensen, Mike R. Dunbar, Robert G. Mclean

Michigan Bovine Tuberculosis Bibliography and Database

Bovine tuberculosis (bTB) is a zoonotic disease caused by Mycobaterium bovis, and is transmissible to humans, wildlife and domestic livestock. In the northern Lower Peninsula of Michigan, white-tailed deer ( Odocoileus virginianus) serve as a reservoir for the disease and pose a significant threat to domestic cattle and captive cervids. Scientists at USDA, APHIS, Wildlife Services, National Wildlife Research Center have designed a variety of laboratory and field studies aimed at reducing or eliminating bTB infection in cattle by interrupting the transmission of the disease from wildlife reservoirs. These strategies include reducing bTB in deer by delivery of …

Research Strategies Of The National Wildlife Research Center To Control Bovine Tuberculosis In Wildlife In Michigan, Usa, A. R. Berentsen, M. R. Dunbary, R. G. Mclean

Michigan Bovine Tuberculosis Bibliography and Database

Bovine tuberculosis (bTB) is a zoonotic disease caused by Mycobaterium bovis and is transmissible to humans, wildlife, and domestic livestock. In the United Kingdom, the suspected wildlife reservoir of bTB is the badger (Meles meles) (HUTCHINGS and HARRIS, 1997), and in New Zealand, the culprit is the brush-tailed possum (Trichosurus vulpecula) (MORRIS et al., 1994). In northern Michigan, USA, bovine tuberculosis is endemic in white-tailed deer (Odocoileus virginianus). In 1975 a hunter-killed white-tailed deer in Alpena County, Michigan, USA, was tested positive for bTB. Subsequent surveillance by the Michigan Department of Natural Resources (MDNR) …

Risk Factors Associated With The Prevalence Of Tuberculosis-Like Lesions In Fenced Wild Boar And Red Deer In South Central Spain, Joaquin Vicente, Ursula Hofle, Joseba M. Garrido, Isabel G. Fernandez-De-Mera, Pelayo Acevedo, Ramon Juste, Marta Barral, Christian Gortazar

Michigan Bovine Tuberculosis Bibliography and Database

In recent decades the management of large game mammals has become increasingly intensive in south central Spain (SCS), resulting in complex epidemiological scenarios for disease maintenance, and has probably impeded schemes to eradicate tuberculosis (TB) in domestic livestock. We conducted an analysis of risk factors which investigated associations between the pattern of tuberculosis-like lesions (TBL) in wild boar (Sus scrofa) and red deer (Cervus elaphus) across 19 hunting estates from SCS and an extensive set of variables related to game management, land use and habitat structure. The aggregation of wild boar at artificial watering sites was …

Vaccination Of White-Tailed Deer (Odocoileus Virginianus) With Mycobacterium Bovis Bacillus Calmette Guerin, M. V. Palmer, T. C. Thacker, W. R. Waters

Michigan Bovine Tuberculosis Bibliography and Database

Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis in domestic livestock. In Michigan, USA tuberculous white-tailed deer transmit M. bovis to cattle. One approach in dealing with this wildlife reservoir is to vaccinate deer in order to interrupt the cycle of deer to deer and deer to cattle transmission. Thirty-one white-tailed deer were assigned to one of three groups; 2 SC doses of 10⁷ CFU of M. bovis BCG (n = 11); 1 SC dose of 10⁷ CFU of M. bovis BCG (n = 10); or unvaccinated deer (n = 10). …

Revisiting The Organohalogens Associated With 1979-Samples Of Brazilian Bees, Walter Vetter, Donald Roberts

Uniformed Services University of the Health Sciences

Brazilian bees of the species Eufriesea purpurata are known to tolerate very high concentrations of DDT. As reported in the literature, these bees have suffered no harm from as much as 2 mg/bee, which is in the per-cent range of the body weight. In 1979, individuals of E. purpurata were captured as they collected DDT from walls of remote, rural houses in Brazil. Reported herein are quantities and identities of DDT, DDT metabolites, and other organohalogen compounds in four samples of bees stored since 1979. The concentrations of DDT (sum of p,p′-DDT, -DDE, and -DDD) ranged from …

Estimating Health Utilities And Quality Adjusted Life Years In Seasonal Affective Disorder Research, Michael C. Freed, Kelly J. Rohan, Brian T. Yates

Uniformed Services University of the Health Sciences

Background: Seasonal affective disorder (SAD) episodes will recur annually without effective intervention. Effectiveness of such interventions is traditionally measured with depression-specific tools (e.g., Beck Depression Inventory 2nd Edition; BDI-II). In a climate of potentially scarce resources, generic outcomes, such as Quality Adjusted Life Years (QALYs), are recommended for cost-effectiveness research. For treatments to be deemed cost-effective, they must show effectiveness relative to each other and relative to interventions across other disorders. To date, QALYs have not been used to determine effectiveness of SAD treatments. Given the recurrent nature of SAD, QALYs, which weight quality of life with time, are an …

Biodosepr-2006 Consensus Committee Report On Biodosimetric Methods To Evaluate Radiation Doses At Long Times After Exposure, Steven L. Simon, Ian Bailiff, André Bouville, Paola Fattibene, Ruth A. Kleinerman, David C. Lloyd, Stephen W.S. Mckeever, Alexander Romanyukha, Alexander V, Sevan’Kaev, James D. Tucker, Albrecht Wieser

Uniformed Services University of the Health Sciences

The requirements for biodosimetric techniques used at long times after exposure, i.e., 6 months to more than 50 years, are unique compared to the requirements for methods used for immediate dose estimation. In addition to the fundamental requirement that the assay measures a physical or biologic change that is proportional to the energy absorbed, the signal must be highly stable over time to enable reasonably precise determinations of the absorbed dose decades later. The primary uses of these biodosimetric methods have been to support long-term health risk (epidemiologic) studies or to support compensation (damage) claims. For these reasons, the methods …

A Statistical Taxonomy And Another “Chance” For Natural Frequencies, Adrien Barton, Shabnam Mousavi, Jeffrey R. Stevens

Department of Psychology: Faculty Publications

Commentary on Barbey & Sloman: "Base-rate respect"

The conclusions of Barbey & Sloman (B&S) crucially depend on evidence for different representations of statistical information. Unfortunately, a muddled distinction made among these representations calls into question the authors’ conclusions. We clarify some notions of statistical representations which are often confused in the literature. These clarifications, combined with new empirical evidence, do not support a dual-process model of judgment.

Personal Values As A Mediator Between Parent And Peer Expectations And Adolescent Behaviors, Laura M. Padilla-Walker, Gustavo Carlo

Department of Psychology: Faculty Publications

The current study examined the mediating role of adolescents’ personal values on the relation between maternal and peer expectations for prosocial behaviors and adolescents’ self-reported prosocial and antisocial behaviors. One hundred thirty-four adolescents (mean age = 16.22 years, 54% girls) completed measures of their own values and behaviors, as well as their perceptions of the positive expectations that their mother and their best friend(s) had for their (the adolescents’) prosocial behaviors. Stepwise regression analyses suggested that adolescents’ personal prosocial values mediated the relation between adolescents’ perceptions of both maternal and peer expectations and adolescents’ prosocial behaviors. In addition, for boys, …

“Introduction” To Modeling Complex Systems: Volume 52 Of The Nebraska Symposium On Motivation, Bill Shuart, William D. Spaulding, Jeffrey Poland

Department of Psychology: Faculty Publications

Capturing the complexity of human behavior has been a recurring theme in the Nebraska Symposium on Motivation:
We expect behavior to be patterned or integrated, and to make biological sense; and so patterning and biological utility are what we see. And of course what we see is actually there-behavior in general is not chaotic; it is organized. (Nissen, 1954, p. 314)
When fundamental psychologists do make excursions into the human motivational world ... it is rare that they survey the requirements for theory or pre-theory by intensive descriptive analysis of behavior related to such motives as produced by concrete human …

Ecological Momentary Assessment Of Older Women's Health, Janice Penrod, Jeremy B. Yorgason, Susan J. Loeb, Chin-Fang Liu, Lesa Hoffman, Sarah H. Gueldner, Leonard W. Poon

Department of Psychology: Faculty Publications

Living with chronic co-morbidities implies long-lasting, always present conditions associated with highly variable health trajectories. In this study, ecological momentary assessment was used to explore nine older women's experiences of living with co-morbidities. Each participant completed a daily diary, which focused on 10 variables related to energy, pain, effort expended, and an overall health rating, for 21 days. Hierarchical linear modeling was used to explore intra-individual variation in daily health experiences and health-related burden, and determine the extent to which health-related burden was related to daily health experiences. Each of the daily health experience variables sipiificantly predicted health-related burden. Over …

Tgfβ3 Inhibits E-Cadherin Gene Expression In Palate Medial-Edge Epithelial Cells Through A Smad2-Smad4- Lef1 Transcription Complex, Ali Nawshad, Damian Medici, Chang-Chih Liu, Elizabeth D. Hay

College of Dentistry: Faculty Publications

Dissociation of medial-edge epithelium (MEE) during palate development is essential for mediating correct craniofacial morphogenesis. This phenomenon is initiated by TGFβ3 upon adherence of opposing palatal shelves, because loss of E-cadherin causes the MEE seam to break into small epithelial islands. To investigate the molecular mechanisms that cause this E-cadherin loss, we isolated and cultured murine embryonic primary MEE cells from adhered or non-adhered palates. Here, we provide the first evidence that lymphoid enhancer factor 1 (LEF1), when functionally activated by phosphorylated Smad2 (Smad2- P) and Smad4 (rather than β-catenin), binds with the promoter of the E-cadherin gene to repress …

Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The retroviral restriction factors, TRIM5α and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5α and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5α, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these B-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5α interaction with the viral capsid, two properties specified by the …

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Differential Engagement Of Tim-1 During Activation Can Positively Or Negatively Costimulate T Cell Expansion And Effector Function, Vijay K. Kuchroo, Sheng Xiao, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Eric Jensen, Jaimie Imitola, Thomas Korn, Ana C. Anderson, Zheng Zhang, Cristina Gutierrez, Thomas Moll, Raymond A. Sobel, Dale T. Umetsu, Hideo Yagita, Hisaya Akiba, Terry Strom, Mohamed H. Sayegh, Rosemarie H. Dekruyff, Samia J. Khoury

School of Veterinary and Biomedical Sciences: Faculty Publications

It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specifi c for Tim-1 and identifi ed two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specifi c T cells, the production of the proinfl ammatory cytokines IFN-γ and IL-17, …

Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo

Jay Reddy Publications

Myelin proteolipid protein (PLP) 139–151 is an immunodominant peptide that induces experimental autoimmune encephalomyelitis (EAE) in H-2^s SJL/J mice. While PLP 139–151-specific TCR transgenic (tg) 4E3 mice develop fulminant spontaneous disease on the susceptible SJL/J background, spontaneous EAE is dramatically reduced on the H-2^s congenic B10.S background. On this resistant background, we observed a high frequency of positively selected tg CD42CD82 (DN) thymocytes and peripheral DN tg T cells. Splenic DN tg T cells responded to anti-CD3 stimulation similarly to CD41 cells, but proliferative and cytokine responses to PLP 139–151 were blunted, implying that CD4 coreceptor down-regulation modulated …

Su.32. Myelin-Specific Regulatory T Cells Accumulate In The Central Nervous System, But Fail To Suppress Pathogenic Effector T Cells At The Peak Of Autoimmune Inflammation [Abstract Only], Thomas Korn, Mohamed Oukka, Jay Reddy, Estelle Betelli, Amit Awasthi, Raymond Sobel, Kai Wucherpfennig, Vijay K. Kuchroo

Jay Reddy Publications

Treatment with ex vivo generated regulatory T cells (Treg) has been regarded as highly attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp “knock-in” mice and myelin oligodendrocyte glycoprotein (MOG)35–55/IAb tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Following immunization with the encephalitogenic peptide MOG35–55 emulsified in complete Freund's adjuvant, MOG35–55-tetramer-reactive, Foxp3+ T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent …