Human immune responses; Viral Immunology; HIV immunopathogenesis; Vaccine-induced immune responses.
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:
Leticia Kuri-Cervantes, Postdoctoral Fellow 2016-. HIV and Influenza specific T cell immunity in humans, T cell dynamics in HIV and SIV infection
Alberto Sada-Japp, Postdoctoral Fellow 2017-. Immunology of Type-1 diabetes, cellular immunity in lymphoid tissues.
Son Nguyen, CAMB MVP Graduate Student 2015-. Mechanisms of immunological control of HIV infection in lymphoid tissue
Vincent Wu, CAMB MVP Graduate Student 2018-. HIV integration sites in lymphoid tissue CD4 cells
Jay Gardner, Lab Manager 2005-
Heidi Gunzelman, Research Specialist 2017-
Steblyanko M, Anikeeva N, Buggert M, Betts MR, Sykulev Y: Assessment of the synaptic interface of primary human T cells from peripheral blood and lymphoid tissue. J. Vis. Exp Page: 137, July 2018.
Buggert M, Nguyen S, Salgado-Montes de OCa G, Bengsch B, Darko S, Ransier A, Roberts ER, Del Alcazar D, Brody IB, Vella LA, Beura L, Wijeyesinghe S, Herati RS, Del Rio Estrada PM, Ablanedo-Terrazas Y, Kuri-Cervantes L, Sada Japp A, Manne S, Vartanian S, Huffman A, Sandberg JK, Gostick E, Nadolski G, Silvestri G, Canaday DH, Price DA, Petrovas C, Su LF, Vahedi G, Dori Y, Frank I, Itkin MG, Wherry EJ, Deeks SG, Naji A, Reyes-Teran G, Masopust D, Douek DC, Betts MR: Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue. Sci. Immunol. 3(24), June 2018.
Sayin I, Radtke AJ, Vella LA, Jin W, Wherry EJ, Buggert M, Betts MR: Spatial distribution and function of T follicular regulatory cells in human lymph nodes. J. Exp. Med. May 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.
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.
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.
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.
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.
Buggert M, Japp AS, Betts MR.: Everything in its right place: resident memory CD8+ T cell immunosurveillance of HIV infection. Current Opinions in HIV and AIDS 2018 Notes: In press.
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.
back to top
Last updated: 05/19/2020
The Trustees of the University of Pennsylvania