Research
T Lymphocyte Development, Activation, and Function
At the present time, there are three active research projects in my laboratory and they are described below.I. Developmental acquisition of IL-4 inducibility
IL-4 presence during antigen encounter causes CD4 T cells to differentiate into Th2 effectors with characteristic IL-4 secretion. Our finding of rapid TCR-triggered IL-4 production by CD1d-independent conventional na?ve CD4 T cells from the thymus prompted us to hypothesize a unique role for these cells in the immune response. Combining molecular, cellular and genetic approaches, our current efforts are directed at identifying the roles played by this relatively small subpopulation of conventional CD4 T cells in allergic response.
II. Generation of CD8 T lymphocyte memory
We have previously shown that a short-term IL-4 exposure during TCR stimulation of na?ve 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 and IL-4R downstream signaling molecules play in the generation and homing patterns of memory cytotoxic cytotoxic T cells. Results from this work may have implications on immune intervention such as tumor immunotherapy and treatment of allergic diseases.
III. Establishing pheno-deviant mouse models through ENU genome-wide mutagenesis
By combining ENU-induced genome-wide mutagenesis in the mouse with a 3-generation breeding scheme, we have identified a collection of over 100 dysmorphology, coat color, liver disease, kidney disease and immunological pheno-deviants. Linkage has been established for roughly half of the identified mutant models and the causative mutant genes have been identified for more than 20 of the models so far. Currently, we are actively cloning mutant genes and characterizing these mutant models.