Contact Info Qizhi Tang, Ph.D. Department of Surgery Box 0780 - HSE 520  513 Parnassus Ave. San Francisco, CA 94143 Ph: (415) 476-1739 Fax: (415) 502-8326 Email: tangq@surgery.ucsf.edu

Assistant Professor

The goal of our research program is to understand the mechanisms of immunological tolerance maintained by a small subset of T cells referred to as regulatory T cells. Currently, our efforts are focused on in vivo analysis of regulatory T cell control of autoimmune diabetes and organ transplant rejection.

Regulatory T cells are vital to immunological tolerance and prevention of autoimmunity. However, these cells represent a very small fraction in the peripheral T cell pool, 5-10% in mouse and 2% in human blood, making it difficult to study. We have developed a robust protocol to expand regulatory T cells in vitro while preserving their immunosuppressive phenotype. The expanded regulatory T cells were able to prevent and even reverse autoimmune diabetes in NOD mice. The availability of a large number of regulatory T cells not only provides a convenient tool to study the biology of these cells, it also makes it more realistic to consider regulatory cell-based immunotherapy for patients suffering from autoimmune diseases. Using these expanded regulatory T cells, combined with cutting edge in vivo imaging technologies such as bioluminescence imaging and two-photon laser scanning microscopy, we have begun to systematically dissect the cellular and molecular processes that underlie diabetes progression and its prevention by regulatory T cells.

Regulatory T cells are also a critical component of transplantation tolerance. However, the level of endogenous regulatory T cells is not sufficient in preventing organ graft rejection. We propose that adoptive therapy using regulatory T cells of the correct specificity in sufficient numbers can be a potent tolerogenic regimen either alone or in combination with other therapies that target the pathogenic T cells. We are testing the therapeutic potential of expanded regulatory T cells isolated from TCR transgenic mice that bear CD4+ T cells specific for alloantigens either directly presented by donor cells or indirectly presented on host cells. In addition, we are analyzing in vivo anti-allograft responses from lymph node priming of T cells to graft destruction using conventional immunological approaches and in vivo imaging technologies. Such analysis will help us to understand the basis for the exceptionally vigorous alloimmune responses and to pinpoint the level of regulatory T cells intervention.

Selected Publications:

Tang Q, Henriksen KJ, Boden EK, Tooley AJ, Subudhi S, Zhang, XX, Strom T, Bluestone JA. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol. 2003 Oct 1;171(7):3348-52.

Tang Q, Boden E, Henriksen, KJ, Bi, M, Jordan HB, Bluestone JA. Distinct roles of CTLA-4 and TGF-ƒÒ in the function of CD4+CD25+ regulatory T cells. Euro. J. Immunol. 2004 Nov;34(11):2996-3005.

Tang Q, Henriksen KJ, Bi M, Finger EB, Szot G, Ye J, Masteller EL, McDevitt H, Bonyhadi M, Bluestone JA. In Vitro-expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes. J Exp Med. 2004 Jun 7;199(11):1455-65.