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Member Information
Michael R. Betts, Ph.D.
Assistant Professor, Department of Microbiology
Office Phone: 215-573-2773
Office Fax: 215-573-4446
Email: betts@mail.med.upenn.edu
Website(s):
Education: Ph.D. 1998, University of North Carolina
Keywords: HIV Immunopathogenesis, Vaccines, Polychromatic Flow Cytometry
Research and/or Clinical Interests:
Dr Betts' lab is interested in understanding the role of the T cell immune response in controlling HIV and other human viral pathogens.
Summary:
My laboratory studies human T lymphocyte function in order to understand the role of these cells in controlling or eliminating viral pathogens and providing protection from infection. Our primary interest is in determining how and if the human CD8 + T cell response to HIV controls viral replication. We also study the immune response against a variety of other human pathogens, including Epstein-Barr virus, cytomegalovirus, influenza, and vaccinia virus. We are also very interested in characterizing the human T cell response to various vaccine regimens against a variety of human pathogens designed to generate cell-mediated immunity in order to understand the underlying principles of vaccine-mediated immune protection.
Human T lymphocytes have numerous functions, including the ability to produce various cytokines and chemokines, as well as mediate cell death through perforin- or fas-mediated cytotoxicity. Our research utilizes the most cutting edge techniques to measure human T lymphocyte responses through the use of polychromatic flow cytometry. This technique allows for the simultaneous examination of up to 18 separate parameters on lymphocytes. By measuring multiple T cell functions simultaneously, we have begun to characterize the complexity of the CD4 + and CD8 + T cell response to HIV, EBV, CMV, Flu, and vaccinia. Not surprisingly, the T cell responses to these different viruses are quite variable; however, common response patterns do exist, and the importance of these patterns in the control of viral replication is the subject of future studies.
Through the use of polychromatic flow cytometry, we are also able to study the memory phenotype of responding virus-specific T cells. This allows us to characterize the nature of immunological memory against chronic viral diseases, such as HIV, CMV, and EBV, and acute viral diseases such as influenza. Characterization of the functional and phenotypic properties of virus-specific T cells allows us to identify immune correlates of protection for use in the development and testing of potential human vaccines.
Representative Publications:
Betts MR, Casazza JP, Patterson BA, Waldrop S, Trigona W, Fu TM, Kern F, Picker LJ, Koup RA. Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype. J Virol. 2000 Oct;74(19):9144-51.
Casazza JP, Betts MR, Picker LJ, Koup RA. Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy. J Virol. 2001 Jul;75(14):6508-16.
Betts MR, Ambrozak DR, Douek DC, Bonhoeffer S, Brenchley JM, Casazza JP, Koup RA, Picker LJ. Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: relationship to viral load in untreated HIV infection. J Virol. 2001 Dec;75(24):11983-91.
Betts MR, Brenchley JM, Price DA, De Rosa SC, Douek DC, Roederer M, Koup RA. Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J. Immunol. Methods 281: 65-78. 2003.
Betts MR, Price DA, Brenchley JM, Lore K, Guenaga J, Smed-Sorenson A, Ambrozak, DR, Migueles S, Connors M, Roederer M, Douek D, Koup RA. The functional profile of primary human antiviral CD8+ T cell effector activity is dictated by cognate peptide concentration. J. Immunol, 172: 6407-6417. 2004.
Price D, West S, Betts MR, Ruff L, Brenchley J, Ambrozak D, Edghill-Smith Y, Kuroda M, Bogdan D, Kunstman K, Letvin N, Franchini G, Wolinsky S, Koup R, Douek D. T-cell receptor recognition motifs govern immune escape by antigenic mutation in acute SIV infection. Immunity 21: 793-803. 2004.
Betts MR, Exley B, Price DA, Bansal A, Comacho ZT, Teaberry V, West SM, Ambrozak DR, Tomaras G, Roederer M, Kilby MJ, Tartaglia J, Belshe R, Gao F, Douek DC, Weinhold KJ, Koup RA, Goepfert P, Ferrari G. Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responss and their role in protection after HIV-1 infection. PNAS 102: 4512-4517. 2005.
Casazza JP, Betts MR, Hill BJ, Brenchley JM, Price DA, Douek DC , Koup RA. Immunologic pressure within class I-restricted cognate Human Immunodeficiency Virus epitopes during HAART. J. Virol, 79:3653-3663. 2005.
Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, Lederman MM, Benito J, Goepfert PA, Connors M, Roederer M, Koup RA. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood E-published on line Feb 7 2006. DOI 10.1182/blood-2005-12-481.
