Biomedical Sciences Graduate Program | University of California, San Francisco

Qizhi Tang, PhD
Regulatory T cell control of autoimmunity and transplant rejection

Selected Publications | Complete Publications

phone	(415) 476-1739
email	tangq@surgery.ucsf.edu
additional websites	(415) 476-1739
secondary research affiliation

Regulatory T cells (Tregs) are a small population of lymphocytes that suppresses the activity of other immune cells. They maintain normal immune homeostasis and safeguard against autoimmune diseases. Their immunosuppressive properties can also be harnessed to control transplant rejection. Research in my laboratory is focused on understanding the action of Tregs in vivo in mouse models of spontaneous Type I Diabetes and solid organ transplant rejection with the goal of developing novel Treg-based cellular therapies for autoimmunity and transplant rejection.

Major research projects:

Regulatory T cell dynamics in autoimmune diabetes. Emerging experimental and clinical evidence suggests Tregs expand as a consequence of immune activation and that such expansion is part of the build-in mechanism for the immune system resolve an immune response after expulsion of the offending pathogens to avoid excessive bystander tissue damage. In a mouse model of type I diabetes, we found Tregs expand in the pancreatic lymph nodes, migrate to islets, but fail to sustain their presence in the islet tissue. The reason for this is a subject of ongoing investigator. Our current result suggest that this is not due to intrinsic defect of Tregs, but likely due to reduced availability of IL-2, an essential survival factor for Tregs.

Functional interplay between pathogenic T cells, Tregs and dendritic cells in autoimmune diabetes. Our recent research findings suggest that Treg interaction with dendritic cells is critical to their in vivo function. We will examine the modulation of dendritic cell functions by islet-reactive pathogenic T cells and Tregs in vivo. Effect of these cells on dendritic cell activation, their ability to process and present self antigens, and alteration of gene expression profiles will be analyzed.

Therapeutic application of Tregs in transplantation. In the settings of organ transplantation, the exceptional vigorous alloreactive immune response often destroys the grafts before Tregs have a chance to expand and control the effector T cells. We propose that adoptive therapy using Tregs of the correct specificity in sufficient numbers can be a potent tolerogenic regimen in combination with other therapies that target the pathogenic T cells . However, therapeutic application of Tregs in the allogeneic transplantation has been limited by the low numbers of these cells and lack of allo-antigen specific Tregs. We will determine the therapeutic potential of in vitro expanded Tregs with various specificities to alloantigens in mouse models of islet and skin transplantation. Efficacy of therapeutic Tregs will be evaluated in conjunction with other immunotherapies. Successful protocols will then be adapted for clinical trial in human patients.

Anatomy of alloimmune response . Alloimmune response is unique in its complexity involving both alloantigens presented by host antigen presenting cells and direct T cell activation by donor antigen presenting cells. Specificity of the T cell response in has not been mapped. We will systematically analyze antigenic specificities and the magnitude of CD4 and CD8 responses in vivo in a mouse model of skin transplantation. The class of the responses, i.e. Th1, Th2, Th3, Th17, Tr1, or Tregs, will be determined. Once the baseline of an alloimmune response has been determined in the skin transplantation model, we will compare it to other organ transplantations such as islet and heart. In addition, the effect of various therapeutic interventions on the repertoire, magnitude, and class of the alloresponses will be assessed.

Selected Publications

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

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, Jun/7/2004;199(11):1455-65.

Bluestone JA, Tang Q Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells. Proc Natl Acad Sci U S A. 101 Suppl 2: 14622-6, Oct/5/2004.

Tang Q, Boden EK, Henriksen KJ, Bour-Jordan H, Bi M, Bluestone JA. Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function. Eur J Immunol, Nov/2004;34(11):2996-3005.

Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P, Santamaria P, Locksley RM, Krummel MF, Bluestone JA. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol, Jan/2006;7(1):83-92.

Tang Q, Bluestone JA Regulatory T-cell physiology and application to treat autoimmunity. Immunol Rev. 212: 217-37, Aug/2006.

Tang Q, Krummel MF Imaging the function of regulatory T cells in vivo. Curr Opin Immunol. 18: 496-502, Aug/2006.

Kang SM, Tang Q, Bluestone JA CD4(+)CD25(+) Regulatory T Cells in Transplantation: Progress, Challenges and Prospects. Am J Transplant. 7: 1457-63, Jun/2007.

information last updated June 2007