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

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

Description of Research Program

Our 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.

One of the major inhibitory effects in clonal 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.

Awards

Merck Award in Chemistry, Soma Weiss Award in Medical Research, U.S. Public Health Service Distinguished Service Medal.

Memberships

• American Association of Immunologists
• Clinical Society of Immunology

Editorial Boards

• Immunity
• Current Opinions in Immunology

Research Group Members

Nevil Singh, Kyungho Choi, Susan McKarns, Satoru Ishihara, Seeyoung Choi, Chuan Chen, Betsy Majane.

Selected Recent Publications

(View current list in PubMed.)

Schwartz, RH. T cell anergy. Annu Rev Immunol. 2003. 21: 305-334.

Singh NJ, Schwartz RH. The strength of persistent antigenic stimulation modulates adaptive tolerance in peripheral CD4+ T cells. J Exp Med. 2003. 198: 1107-1117.

Bruniquel D, Schwartz RH. Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nature Immunol. 2003. 4: 235-240.

Schwartz RH, Mueller DL. Immunological Tolerance. In Paul WE, ed. Fundamental Immunology. Philadelphia: Lippincott, Williams & Wilkins; 2003: 901-934.

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