Fink, Pamela

There are currently two main areas of study in the Fink laboratory. First, a line of TCR Vß5 transgenic mice has been used to study the induction of self tolerance among mature peripheral T cells. An age-dependent deletion of populations of transgenic T cells results from encounter with a self antigen. In addition, tolerogen encounter drives some CD4+ T cells to reexpress the recombination machinery, resulting in rearrangement and expression of endogenous TCRß chain genes. Cells that express a novel TCR are rescued and are fully immunocompetent. Current work is focused on understanding the mechanism of TCR revision, the process of inducing tolerance through expression of alternate TCRs. The second area of study is the analysis of recent thymic emigrants (the youngest peripheral T cells) from mice carrying a transgene for green fluorescent protein driven by the RAG2 promoter. T cells complete both functional and phenotypic maturation in the lymphoid periphery, and current investigation centers on the signals provided by the peripheral environment that promote this post-thymic phase of T cell maturation and on the details of the observed functional defects. Using a diabetes model system, we are also testing whether recent thymic emigrants are more easily tolerized than more mature peripheral T cells.