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Ronald H. Schwartz, M.D., Ph.D.
Building 4, Room 211C
4 Memorial Drive
Bethesda, MD 20892-0420
Phone: 301-496-1257
Fax: 301-496-0877
rschwartz@mail.nih.gov

Laboratory of Cellular and Molecular Immunology

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Ronald H. Schwartz, M.D., Ph.D.

Photo of Ronald H. Schwartz, M.D., Ph.D.

Chief, Laboratory of Cellular and Molecular Immunology
Chief, T-Cell Activation Section, LCMI

Major Areas of Research

  • T-cell anergy, tolerance, and activation
  • Molecular regulation of interleukin 2 gene expression
 

Program Description

This laboratory discovered the phenomenon of T-cell anergy and has been interested over the past 15 years in understanding its molecular basis and its in vivo relevance in murine model systems. We are currently using molecular biology and protein biochemistry approaches to characterize the molecules responsible for the induction and maintenance of T-cell clonal anergy in vitro.

At the same time, we have developed an in vivo anergy model using CD4+ T cells from T-cell receptor (TCR) transgenic mice transferred into a second transgenic mouse expressing the antigen. The anergic state that develops, which we call adaptive tolerance, appears to involve a receptor desensitization process distinct from clonal anergy. We are actively pursuing the molecular mechanisms behind this state and the process by which it is induced. The double transgenic mice also develop a mild form of chronic arthritis, whose pathogenesis we are attempting to elucidate. In particular, we are studying the impact of the commensal gut flora on the severity of the disease.

One of the major inhibitory effects in anergy is the down-regulation of IL-2 gene transcription. In studying this process, we serendipitously discovered that the promoter region of the IL-2 gene in naïve T cells is rapidly and selectively demethylated by an active process following TCR stimulation. This has led us into a characterization of chromatin structural changes occurring in several cytokine genes during T-cell development. In the past few years this area has become a second major focus of research in the laboratory.

Biography

Dr. Schwartz graduated from Cornell University with a B.S. in chemistry (summa cum laude) in 1965. He graduated cum laude from Harvard Medical School in 1970. He completed a Ph.D. at the Institute of Microbiology in 1973 on the interaction of synthetic polypeptides with macrophage RNA. He came to NIH in 1972 and was appointed as a staff scientist in the U.S. Public Health Service, working on separation procedures for cells in the immune system.

In 1974, Dr. Schwartz was appointed a research associate in the NIAID Laboratory of Immunology, where he began his work on immune response gene control of T-cell proliferative responses in mice. He became a tenured senior investigator in 1976 and subsequently made a number of seminal observations on the nature of the processed antigen recognized by T cells.

In 1986, he became chief of the Laboratory of Cellular and Molecular Immunology and subsequently discovered the tolerance phenomenon of T-cell clonal anergy. His laboratory also discovered the CD4 natural killer (NK) T cell. He is currently working on understanding an in vivo model of T-cell anergy called adaptive tolerance and dissecting the regulation of interleukin-2 gene activation in CD4+ T cells.

Awards

Merck Award in Chemistry, Soma Weiss Award in Medical Research, U.S. Public Health Service Distinguished Service Medal, American Association for the Advancement of Science (AAAS) Fellow

Memberships

  • American Association of Immunologists
  • Clinical Society of Immunology

Editorial Boards

  • Immunity
  • Current Opinions in Immunology

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Research Group

Nevil Singh
Pascal Chappert
Seeyoung Choi
Liangtang Wu
Charles Mainhart
Eleanore Chang
Quan Zheng

Selected Publications

Ishihara S, Schwartz RH. Two-step binding of transcription factors causes sequential chromatin structural changes at the activated IL-2 promoter. J Immunol. 2011 Sep 15;187(6):3293-9.

Choi S, Schwartz RH. Impairment of immunological synapse formation in adaptively tolerant T cells. J Immunol. 2011 Jul 15;187(2):805-16.

Chappert P, Schwartz RH. Induction of T cell anergy: integration of environmental cues and infectious tolerance. Curr Opin Immunol. 2010 Oct;22(5):552-9.

Ishihara S, Varma R, Schwartz RH. A new fractionation assay, based on the size of formaldehyde-crosslinked, mildly sheared chromatin, delineates the chromatin structure at promoter regions. Nucleic Acids Res. 2010 Jun 1;38(11):e124.

Johnson AL, Aravind L, Shulzhenko N, Morgun A, Choi SY, Crockford TL, Lambe T, Domaschenz H, Kucharska EM, Zheng L, Vinuesa CG, Lenardo MJ, Goodnow CC, Cornall RJ, Schwartz RH. Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection. Nat Immunol. 2009 Aug;10(8):831-9.

McKarns SC, Schwartz RH. Biphasic regulation of Il2 transcription in CD4+ T cells: roles for TNF-alpha receptor signaling and chromatin structure. J Immunol. 2008 Jul 15;181(2):1272-81.

Visit PubMed for a complete publication list.

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Last Updated March 27, 2013