Chih-Pin Liu, Ph.D. Research

T-cells and Immunity
T-cells play a central role in the generation of the host’s immunity to infections and tumors, and in the regulation of autoimmunity and allergy.  A critical prerequisite for selection and maturation of T-cells is cell surface expression of the T-cell antigen receptor (TCR) complex, which is responsible for recognition of antigens and for transmitting signals inside the cell. These processes are regulated by the interaction of TCR with antigens presented by major histocompatibility complex (MHC) molecules expressed on antigen presenting cells. Research carried out in this laboratory investigates the molecular and cellular mechanisms underlying T-cell mediated immunity against tumors and the roles of T-cells in regulating inflammatory and autoimmune diseases.

Mechanisms underlying T-cell-mediated Immunity
Recognition of the MHC/antigen complex by TCRs generates a series of signaling events that regulate the behavior and function of T-cells. To study the molecular and cellular mechanisms regulating T-cell mediated immunity, we will use state-of-art molecular and proteomics (the study of proteins) approaches to identify the molecules regulating the activation and apoptosis of normal T cells and T cell leukemia. We will also investigate the in vivo role of these molecules using transgenic and gene knockout mice. These proteins may serve as molecular targets for modulating the function of T-cells and for the further immunotherapeutic treatment of various types of cancers. Moreover, we will perform experiments to determine the mechanisms that regulate T-cell functions responsible for tumor immunity and autoimmunity.

Regulation of Autoimmune Disease
In autoimmune diseases, such as type 1 diabetes, presentation of autoantigens by disease-associated MHC plays a critical role in the selection and activation of disease-associated T-cells.  It is now known that T-cells not only function as pathogenic T-cells that cause the disease but also function as regulatory T-cells that inhibit the disease. It has been shown that antigen-specific regulatory T-cells are more potent than a heterogeneous population of regulatory T cells in suppressing pathogenic processes. Therefore, it is desirable to use antigen-specific regulatory T cells to modulate the function of pathogenic T-cells to prevent autoimmune disease. It has been historically very difficult for immunologists to identify and isolate a sufficient number of antigen-specific T cells for further studies. We have addressed this question using novel multivalent MHC/ antigen tetramers, and have identified and isolated several lines of antigen-specific regulatory T-cells. We have demonstrated that the isolated regulatory T-cells can effectively inhibit type 1 diabetes.  Based on these findings, we will investigate the molecular and cellular mechanisms underlying the regulation of pathogenic T cell by these regulatory T cells that lead to prevention of the disease.  We will also examine whether these potent regulatory T cells can be used as a treatment to prevent the immune destruction of islet grafts in an animal model for islet transplantation.