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Dr Wendy BrownSpeaker Biography

Dr. Wendy Brown

Dr. Wendy C. Brown is recognized internationally for her research on bovine T lymphocyte responses to tick-borne pathogens of cattle. She is a Regents Professor in the Department of Veterinary Microbiology and Pathology at Washington State University. She received her BA degree in Microbiology from Smith College, MPH degree in Infectious Disease Epidemiology from Yale University, and PhD degree in Immunology from Yale University. Her research has two major thrusts. One is the use of CD4 T lymphocytes to identify promising vaccine antigens for bovine protozoal parasites Theileria parva and Babesia bovis, and the rickettsial pathogen Anaplasma marginale, with a focus on subdominant and strain conserved protein antigens. She is exploring the role of CD4 T cells in providing long-term memory CD8 cytotoxic T cell responses to T. parva. The second focus is on understanding how these pathogens persist in the face of an immune response. She has discovered that infection with A. marginale causes exhaustion and deletion of CD4 T cells primed by immunization and is trying to determine the mechanism.

Dr. Brown's research has been supported by the National Institutes of Health-National Institute of Allergy and Infectious Diseases, the United States Department of Agriculture-National Institute of Food and Agriculture, and the Bill and Melinda Gates Foundation. Dr. Brown has served on many USDA Animal Health and Well-Being panels and NIH study sections including Microbiology and Infectious Diseases that reviews career development awards. She is a recipient of the International Veterinary Immunologist Award.

Abstract Submission

Exhausted CD4 T-cell Response Induced by Anaplasma marginale

Department of Veterinary Microbiology and Pathology
College of Veterinary Medicine, Washington State University, Pullman, WA, USA

Anaplasma marginale is a tick-transmitted, intra-erythrocytic rickettsial pathogen of cattle that causes anemia and mortality. Cattle that survive acute disease remain persistently infected with fluctuating high levels of bacteremia. Failure to clear infection is due in part to antigenically variant major surface proteins (MSPs) but we propose persistence also results from CD4 T-cell exhaustion during high pathogen load. Following A. marginale infection, cattle previously immunized with MSPs developed a progressive loss of T-cell proliferation and IFN-? and TNF- secretion. Exhaustion was reversed after clearing the infection with tetracyclines. Exhaustion led to deletion of tetramer+ve CD4 T cells from peripheral blood, and although small numbers of antigen-specific CD4 T cells were detected in lymphoid organs and liver, functional T cells could not be recovered. We hypothesized that A. marginale infection induced regulatory T cells. Furthermore, we proposed that CD4 T-cell exhaustion following infection would require the presence of the T-cell antigen, used for immunization, on the infecting bacteria. Cattle were immunized with MSP1a containing a DRB3*1101-restricted T cell epitope and potential regulatory FoxP3+ and ?δ part T cell subsets in blood and spleen were enumerated by flow cytometry following infection with either A. marginale expressing the T-cell epitope, or A. marginale subsp. centrale lacking the epitope. Loss of the MSP1a-specific T-cell response occurred only after infection with A. marginale, and was not associated with an increase in T cells with a regulatory phenotype. Current research is examining the induction of inhibitory T-cell receptors PD-1 and LAG-3 and the ligand PD-L1 following infection.

This research was supported by USDA-NIFA 2010-65119-20456 and NIH NIAID AI-053692

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