An encounter with a foreign pathogen or antigen stimulates naive T lymphocyte activation and the generation of immunologic memory. The T cells which are responsible for immunologic memory differ, both phenotypically and functionally, from naive T cells. Of interest is the observation that aging is associated with an enhanced level of memory T cells, suggesting that the qualitative T cell response differs in the elderly. Further, differences in the proportion of memory to naive T cells may be responsible for immune dysfunction and autoimmunity associated with the aging process. In general, the goal of our research is to characterize the differences between antigenically naive (virgin) and memory T helper cells at the developmental, phenotypic, and functional levels. We have a particular interest in the study of the collaborative interaction between B and T lymphocytes which leads to immunoglobulin secretion ie. the ability of either virgin or memory T cells to promote the activation and differentiation of antigen-specific B cells. We are also actively studying the differential susceptibility of virgin and memory T cells to activation and tolerance signals, which has potential implication with respect to autoimmunity. Culture with superantigens, such as SEB, can lead to profound stimulation, death, or anergy, depending on the differentiation state of the T cell. We have shown that memory T cells differ from naive T cells in their response to SEB, as memory T cell activation is specifically suppressed. We are currently examining intracellular signal transduction pathways and initiated in response to SEB and peptide antigen. We are also examining extracellular influences (eg. costimulation) on T cell subset activation and function. Comparisons are made between the responses of virgin and memory T cells to antigen vs superantigen.