Immune activation induces a strong expansion of antigen-specific T cells that acquire effector functions and control spread of invading pathogens. During recovery from infection most activated T cells die but a fraction remains and returns to a resting state. These memory cells provide improved immunological protection to a future challenge with the same pathogen. Our studies have two aims: 1 To clarify the role of TNF-R superfamily members in regulating effector, memory and regulatory T cell formation in vivo. For these studies we have generated a unique series of transgenic mice that overexpress the specific ligands for two receptors i.e. CD27 and GITR. 2 To delineate genetic programs that direct CD8+ T cell differentiation and test if interference with particular differentiation pathways impedes establishment of immunological memory. To identify genes that are expressed during specific differentiation stages transcriptomes of CD8+ T cell subsets were compared by Agilent® micro array analyses and 267 genes were selected that were significantly up or downregulated in effector-type cells compared to naïve and/or memory-type cells. Importantly an evolutionary-conserved novel transcription factor was identified that appears to selectively expressed in cytolytic T cells and NK cells. The function of this factor is currently being analyzed.