Immunology Graduate Group

Steven L. Reiner, M.D.
Chair, Immunology Graduate Group
Professor, Abramson Family Cancer ResearchInstitute

and Department of Medicine, Division of Infectious Diseases

Address

421 Curie Blvd., BRBII/III, Room 414
Philadelphia, PA 19104
Office Phone: 215-746-5536
Fax: 215-746-5525
Email: sreiner@mail.med.upenn.edu

Education
M.D., Duke University
B.A., Haverford College

Research Interests

Host response to infectious diseases; effector and memory T lymphocyte differentiation; asymmetric cell division; epigenetic and transcription factor-mediated control of gene expression

Research Summary
 
The Reiner laboratory studies how the extrinsic and intrinsic signals are coupled to specify the T lymphocyte fates that are required for immunity. The simultaneous tasks of division, differentiation, diversification, and 4-dimensional navigation by the naïve T cell and its immediate cellular progeny during the immune response make this an exciting problem of developmental biology, cellular adaptation to environmental variables, and the propagation of signaling pathways through space and time.  Using infectious disease models, we are examining the critical sequence-specific transcription factors of the major CD4+ and CD8+ T effector and memory T cell fates and how these factors couple growth factor responsiveness and inheritable patterns of gene expression.  Approaches to study asymmetric cell division include static and time-lapsed imaging, genetic, and biochemical methods to better understand the nature and extent of this ancient diversification process. It is anticipated that study of T cell differentiation during the immune response will continue to become an increasingly useful model for inquiry into the fundamental problem of regulated gene expression in dividing, differentiating, and highly mobile cells. Such studies should also illuminate a novel set of pathways that can be targeted for enhancing or diverting the immune response.

Recent Publications

Mullen, A.C., F.A. High, A.S. Hutchins, H.W. Lee, A.V. Villarino, D.M. Livingston, A.L. Kung, N. Cereb, T.P. Yao, S.Y. Yang, and S.L. Reiner. 2001. Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292:1907-1910.

Hutchins, A.S., A.C. Mullen, H.W. Lee, K.J. Sykes, F.A. High, B.D. Hendrich, A.P. Bird, and S.L. Reiner. 2002. Gene silencing quantitatively controls the function of a developmental trans-activator. Mol Cell 10:81-91.

Mullen, A.C., A.S. Hutchins, F.A. High, H.W. Lee, K.J. Sykes, L.A. Chodosh, and S.L. Reiner. 2002. Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction. Nat Immunol 3:652-658.

Pearce, E.L., A.C. Mullen, G.A. Martins, C.M. Krawczyk, A.S. Hutchins, V.P. Zediak, M. Banica, C.B. DiCioccio, D.A. Gross, C.A. Mao, H. Shen, N. Cereb, S.Y. Yang, T. Lindsten, J. Rossant, C.A. Hunter, and S.L. Reiner. 2003. Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302:1041-1043.

Intlekofer, A.M., N. Takemoto, E.J. Wherry, S.A. Longworth, J.T. Northrup, V.R. Palanivel, A.C. Mullen, C.R. Gasink, S.M. Kaech, J.D. Miller, L. Gapin, K. Ryan, A.P. Russ, T. Lindsten, J.S. Orange, A.W. Goldrath, R. Ahmed, and S.L. Reiner. 2005. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 6:1236-1244.

Takemoto, N., A.M. Intlekofer, J.T. Northrup, E.J. Wherry, and S.L. Reiner. 2006. Cutting Edge: IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation. J Immunol 177:7515-7519.

Chang, J.T., V.R. Palanivel, I. Kinjyo, F. Schambach, A.M. Intlekofer, A. Banerjee, S.A. Longworth, K.E. Vinup, P. Mrass, J. Oliaro, N. Killeen, J.S. Orange, S.M. Russell, W. Weninger, and S.L. Reiner. 2007. Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315:1687-1691.

Intlekofer, A.M., N. Takemoto, C. Kao, A. Banerjee, F. Schambach, J.K. Northrop, H. Shen, E.J. Wherry, and S.L. Reiner. 2007. Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells. J Exp Med 204:2015-2021.

Reiner, S.L. 2007. Development in motion: helper T cells at work. Cell 129:33-36.

Reiner, S.L., F. Sallusto, and A. Lanzavecchia. 2007. Division of labor with a workforce of one: challenges in specifying effector and memory T cell fate. Science 317:622-625.

 

 

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