Regulatory/Suppressor T Cells

Organizer(s): Ethan M. Shevach and Luciano Adorini

Sponsored in part by the Director's Sponsor Fund

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Summary of Meeting:

Although the concept of suppression mediated by T lymphocytes was originally proposed more than 30 years ago, recent studies in animal models of autoimmunity have rekindled interest in the existence of a subset of lymphocytes that specifically suppress immune responses. One population of naturally-occurring or endogenous T suppressor cells can be identified by co-expression of the CD4 and CD25 antigens. These cells suppress the activation of CD4 and CD8 T cells in vitro by an unknown cell-contact dependent mechanism. In vivo, these cells suppress autoimmune disease by both cell contact-dependent and suppressor cytokine-dependent pathways. Although these cells were originally described in the mouse, a population with identical phenotypic and functional properties has been identified in man. A second group of suppressor cells can be induced in vivo by oral exposure to antigen, by culture of T cells with cytokines (IL-10), or by pharmacologic manipulation of dendritic cell functions. These antigen-induced suppressors primarily inhibit T cell activation in vitro and in vivo by secreting suppressor cytokines. Determination of the cellular target and the molecular basis of CD4+CD25+ mediated suppression is a major area of current research. The nature of the physiologic ligand recognized by these cells is also unknown as is the breadth of their T cell repertoire. Suppressor/regulatory T cells have primarily been shown to inhibit animal models of autoimmune disease. However, recent studies have extended their range of activities to inhibition of tumor immunity, graft rejection, allergic disease, graft versus host disease, and acute and chronic infectious diseases. One critical area of future study will involve the development of protocols to enhance regulatory T cell function in vivo by pharmacologic means as such an approach should prove useful in autoimmunity, allergic disease, and graft rejection. Similarly, a related area will involve inhibition of regulatory T cell function, either transiently or permanently, by pharmacologic manipulation or treatment of animals or man with monoclonal antibodies specific for effector molecules on these cells. Protocols are now being developed for the adoptive immunotherapy of both CD4+CD25+ T cells that have been expanded in vitro and for suppressor cells that have been induced in vitro. These cells will be administered to patients with GVHD, graft rejection, and organ-specific and systemic autoimmune disease. This meeting will review all of the above issues and focus on the manipulation of regulatory T cell function in animal models of human disease as well as in disease in man.

Discounted Abstract Deadline: November 10 2003

Discounted Registration Deadline: January 12 2004

We gratefully acknowledge additional support for this conference from:

We gratefully acknowledge the generous grant for this conference provided by:

National Cancer Institute (NCI)
Grant No. 1R13CA105864-01

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