MHC-II-restricted CD4+ T cells with diverse TCR repertoire play critical helper functions in the initiation of cell-mediated immunity as well antibody response. In order to perform effector function, most CD4+ T cells need to go through "priming", a process that usually takes several days. We have found that there exist two types of innate CD4+ T cells, both with diverse TCR repertoire. One type is capable of rapidly producing Th2 cytokines and the other type is capable of rapidly producing Th1 cytokines. We are actively studying the development and function of these innate CD4+ T cell subsets.
We have previously shown that a short-term IL-4 exposure during TCR stimulation of naïve CD8 T cells resulted in the generation of long-lived and functional cytotoxic T cell memory. This result supports the concept that T cell longevity can be determined at the time of antigen encounter and that the high efficiency in vitro memory induction system we have established is a valuable tool in the analysis of cellular and molecular mechanisms of memory development. At the present time, our efforts are focused on the cellular and molecular mechanisms various costimulatory molecules play in the generation and homing patterns of memory cytotoxic T cells. Results from this work may have implications on immune intervention such as tumor immunotherapy and treatment of allergic diseases.
Using ENU-induced genome-wide mutagenesis, we have a number of mutant mouse strains suitable for studying lymphocyte development and function. Two mutant models that possess variant hypomorphic Zap70 and H2-Aa alleles are being studied. The hypomorphic Zap70 mutant spontaneously produce autoantibody and we are actively investigating the mechanism that leads to autoantibody production. While B cell development takes place in the H2-Aa mutant, they are unresponsive to B cell receptor stimulation and we are actively investigating the mechanism responsible for the development of the dysfunctional B cells.