Our research focuses on the regulation of T-cell responses, and the signals that determine the choice between effector and regulatory cells and between lymphocyte activation and tolerance. We exploit a large panel of transgenic and knockout mouse strains to address fundamental questions in three related areas.

1. Systemic tolerance and autoimmunity. Using a novel model of systemically expressed self-antigen, we are studying the mechanisms of intrinsic T-cell anergy and how it breaks down, resulting in autoimmunity. We are also identifying the stimuli involved in the generation of thymic and peripheral regulatory T-cells, and how these signals alter the balance of effector and regulatory cells. We are studying the role of cellular competition in the maintenance of self-tolerance, and the mechanisms underlying the association of lymphocyte deficiency and autoimmunity.

2. Memory T-cell development. The goal of this project is to define the signals that promote the development of memory cells, and how these signals overcome cell death. Emphasis is on the role of the cytokines IL-2 and IL-7, and the transcription factors that are activated by these cytokines.

3. Functions of interleukin-2 (IL-2). The prototypic T-cell growth factor, IL-2, plays an obligatory role in controlling immune responses by maintaining CD25+ Fox P3+ regulatory T-cells. In this project, we use mice lacking IL-2 and the a chain of the IL-2 receptor to define the role do this cytokine in the survival and functional activities of Treg. We also study the autoimmune disease of IL-2–knockout mice, and the ability of costimulator and cytokine antagonists to block development of this disease.

Lohr J, Knoechel B, Jiang S and Abbas AK. The inhibitory function of endogenous B7 costimulators in immune responses. Nature Immunology 2003; 4:664-669.

Andres P, Howland K, Nirula A, Kane LP, Barron L, Dresnek D, Sadra A, Imboden J, Weiss A and Abbas AK. Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation. Nature Immunology 2004; 5:435-442.

Eggena ME, Walker LS, Nagabhushanam V, Barron L, Chodos A and Abbas AK. CTLA-4 and regulatory T cells cooperate to maintain tolerance to a tissue antigen. J. Exp. Med. 2004;199:1725-1730.

Knoechel B, Lohr J, Kahn E, Bluestone JA, and Abbas AK. Sequential development of effector and regulatory T lymphocytes in response to endogenous systemic antigen. J. Exp. Med. 202:1375-1386, 2005.

Rioux JD, and Abbas AK. Paths to understanding the genetic basis of autoimmune disease. Nature Insight 2005; 435:2-7.

Abbas AK and Lichtman AH. CELLULAR AND MOLECULAR IMMUNOLOGY. Elsevier, Philadelphia. 5th edition, updated 2005. (1st edition published in 1991)

Abbas AK and Lichtman AH. BASIC IMMUNOLOGY; Functions and Disorders of the Immune System. Elsevier, Philadelphia. 2nd edition, 2004, updated 2006. (1st edition published in 2001)

Kumar V, Abbas AK, Fausto N. ROBBI NS & COTRAN PATHOLOGIC BASIS OF DISEASE. W. B. Saunders. 7th edition, 2004.