Perelman School of Medicine at the University of Pennsylvania

Penn Institute for Immunology

Michael R. Betts

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Associate Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
402C Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
Office: 215-573-2773
Fax: 215-573-4446
BS (Zoology)
University of Maryland, 1990.
PhD (Microbiology and Immunology)
University of North Carolina, 1998.
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Description of Research Expertise

Research Interests
Human immune responses; Viral Immunology; HIV immunopathogenesis; Vaccine-induced immune responses.

Key words: HIV; T cell; Immune Response

Description of Research
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. Importantly, the techniques we utilize can be applied to the study of the cell-mediated immune response against any human pathogen, including emerging pathogens and bioterrorism agents. 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 can 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.

The current direction within the lab is to determine the underlying mechanisms that control the cell fate and functional characteristics of HIV-specific T and B cells in the context of HIV infection and disease progression. Current studies in the lab in this regard are listed below with Laboratory personnel:

Lab personnel:
Morgan Reuter-Moslow, Postdoctoral Fellow. HIV-specific T cell immunity. T cell function in human lymph nodes; CD200-CD200R pathway interactions in human T lymphocytes.

Laura McLane, Postdoctoral Fellow. Expression, localization, and biochemical properties of the transcription factors T-bet and Eomesodermin within human T lymphocytes.

Korey Demers, Graduate Student-CAMB MVP. Role of T-bet and Eomesodermin transcription patterns in CD8+ T cell mediated control of HIV infection during acute and chronic infection.

Carolina Pombo Martinez, Graduate Student-CAMB MVP. Expression patterns of inhibitory receptors in human T cells in peripheral blood and lymph node in the context of HIV infection.

Irene Bukh, Graduate Student-VMD/PHD, CAMB MVP. Vaccine induced immune activation in rhesus macaques and SIV infection susceptibility.

Jamie Knox, Graduate Student- CAMB MVP. B cell dynamics in HIV infection. T-bet expression and function in B cell subsets in humans.

Emily Roberts, Graduate Student- IGG. Immune activation and SIV-specific CD4+ and CD8+ T cell response development in acute SIV infection.
Jay Gardner, Research Specialist

Selected Publications

Buggert M, Nguyen S, McLane LM, Steblyanko M, Anikeeva N, Paquin-Proulx D, Del Rio Estrada PM, Ablanedo-Terrazas Y, Noyan K, Reuter MA, Demers K, Sandberg JK, Eller MA, Streeck H, Jansson M, Nowak P, Sönnerborg A, Canaday DH, Naji A, Wherry EJ, Robb ML, Deeks SG, Reyes-Teran G, Sykulev Y, Karlsson AC, Betts MR.: Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease. PLoS Pathog. 14(4), April 2018.

Wendel BS, Del Alcazar D, He C, Del Río-Estrada PM, Aiamkitsumrit B, Ablanedo-Terrazas Y, Hernandez SM, Ma KY, Betts MR, Pulido L, Huang J, Gimotty PA, Reyes-Terán G, Jiang N, Su LF.: The receptor repertoire and functional profile of follicular T cells in HIV-infected lymph nodes. Sci Immunol. 3(22), April 2018.

Voillet V, Buggert M, Slichter CK, Berkson JD, Mair F, Addison MM, Dori Y, Nadolski G, Itkin MG, Gottardo R, Betts MR, Prlic M.: Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions. JCI Insight. 3(7), April 2018.

Abdel-Mohsen M, Kuri-Cervantes L, Grau-Exposito J, Spivak AM, Nell RA, Tomescu C, Vadrevu SK, Giron LB, Serra-Peinado C, Genescà M, Castellví J, Wu G, Del Rio Estrada PM, González-Navarro M, Lynn K, King CT, Vemula S, Cox K, Wan Y, Li Q, Mounzer K, Kostman J, Frank I, Paiardini M, Hazuda D, Reyes-Terán G, Richman D, Howell B, Tebas P, Martinez-Picado J, Planelles V, Buzon MJ, Betts MR, Montaner LJ.: CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. Sci Transl Med. 10(437), April 2018.

Noyan K, Nguyen S, Betts MR, Sönnerborg A, Buggert M.: Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells. Front Immunol. 9(19), January 2018.

Reuter MA, Del Rio Estrada PM, Buggert M, Petrovas C, Ferrando-Martinez S, Nguyen S, Sada Japp A, Ablanedo-Terrazas Y, Rivero-Arrieta A, Kuri-Cervantes L, Gunzelman HM, Gostick E, Price DA, Koup RA, Naji A, Canaday DH, Reyes-Terán G, Betts MR.: HIV-Specific CD8+ T Cells Exhibit Reduced and Deferentially Regulated Cytolytic Activity in Lymphoid Tissue. Cell Rep. 21(12): 3458-3470, December 2017.

Knox, J.J., Buggert, M., Kardava, L., Seaton, K.E., Eller, M.A., Canaday, D.H., Robb, M.L., Ostrowski, M.A., Deeks, S.G., Slifka, M.K., Tomaras, G.D., Moir, S., Moody, M.A., Betts, M.R.: T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response. JCI Insight 2(8): 92943, April 2017.

Petrovas, C., Ferrando-Martinez, S., Gerner, M.Y., Casazza, J.P., Pegu, A., Deleage, C., Cooper, A., Hataye, J., Andrews, S., Ambrozak, D., Del Río Estrada, P.M., Boritz, E., Paris, R., Moysi, E., Boswell, K.L., Ruiz-Mateos, E., Vagios, I., Leal, M., Ablanedo-Terrazas, Y., Rivero, A., Gonzalez-Hernandez, L.A., McDermott, A.B., Moir, S., Reyes-Terán, G., Docobo, F., Pantaleo, G., Douek, D.C., Betts, M.R., Estes, J.D., Germain, R.N., Mascola, J.R., Koup, R.A.: Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Science Translational Medicine 9(373), 2017.

Knox, JJ, Kaplan, DE, Betts, MR: T-bet-expressing B cells during HIV and HCV infections. Cell Immunol. 2017 Notes: Epub ahead of print 2017.

Calcedo, R., Somanathan, S., Qin, Q., Betts, M.R., Rech, A.J., Vonderheide, R.H., Mueller, C., Flotte, T.R., Wilson, J.M.: Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency. Proceedings of the National Academy of Sciences of the United States of America 114(7): 1655-1659, 2017.

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Last updated: 05/02/2018
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