Qizhi Tang, PhD

Associate Professor
Director, Transplantation Research Laboratory

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Description of Research
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 1 diabetes and solid organ transplant rejection with the goal of developing novel Treg-based cellular therapies for autoimmunity and transplant rejection.

Major research projects:

Functional interplay between pathogenic T cells, Tregs and dendritic cells in autoimmune diabetes. 
Our previous research findings suggest that Treg interaction with dendritic cells is critical to their in vivo function.  We are combining dynamic imaging, cellular immunology, and molecular biology approaches to examine the modulation of dendritic cell functions by islet-reactive pathogenic T cells and Tregs in vivo.

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 cellular 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.

Immunobiology of stem cell transplantation
Stem cell therapy offers exiting opportunities as an alternative or an adjunct treatment to organ transplantation due to their ability to regenerate and their purported immunosuppressive and tissue repair properties.  This project focuses on analyzing the in vivo immunogenicity of allogeneic mouse mesenchymal stem cells to dissect the cellular and molecular mechanisms of stem cell-mediated immunosuppression.  Additionally, we are investigating the ability of mesenchymal stem cells to promote engraftment of syngeneic and allogeneic islet transplantation in mouse models. 

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.