Our laboratory studies the molecular mechanisms involved in the specification of distinct T lymphocyte lineages during development in the thymus and in response to microbial challenge in peripheral tissues. Elucidation of these mechanisms will help us to understand how normal protective immune responses differ from pathogenic ones that result in inflammation and autoimmune disease. Our studies on thymocytes are focused on how they are specified to differentiate towards either the helper or cytotoxic lineages. We are characterizing the transcription factors involved in lineage specification and in regulation of CD4 and CD8 gene expression, with emphasis on mechanisms for establishing epigenetic programs in maturing T cells.