Time: December 3, 2009 (Thursday), 5:30 pm - 7:30 pm

Place: 9th Floor Conference Room (9S235) of Bldg. 10, NIH-Bethesda Campus

1. Dr. Maria Laura Allende (NIDDK, NIH), 5:30 pm

"S1P1 receptor function during development and immunity"

2. Dr. Jung-Hyun Park (NCI, NIH), 6:30 pm

"Cytokine signaling is necessary to specify CD8-lineage choice and to direct CD8 T cell differentiation during T cell development in the thymus",

Sphingosine-1 phosphate (S1P) is a product of the sphingolipid metabolism, formed via the phosphorylation of sphingosine by sphingosine kinases and it has an important role as a cellular singnaling molecule. S1P regulates diverse cellular functions through a family of G-protein coupled receptors. S1P1 was the first receptor to be identified and cloned. After binding S1P, S1P1 activates a Gi- mediated signaling pathway that is fundamental for proliferation, cell migration, and morphogenesis. Deletion of the gene coding for S1P1 has uncovered its essential function during embryonic vascular development and in immunity.

2."Cytokine signaling is necessary to specify CD8-lineage choice and to direct CD8 T cell differentiation during T cell development in the thymus"

T cell receptor (TCR) signaling in pre-selection double positive (DP) thymocytes initiates a selection process that culminates in the positive selection as well as lineage choice of immature thymocytes into mature CD4+ helper and CD8+ cytotoxic cells. The precise mechanism how this is achieved is still under dispute but it has been proposed that either quantitative or qualitative differences in TCR signaling only would account for the different outcomes of lineage choice. In contrast to such views, here we show that TCR signaling alone is not sufficient to determine cell fate of developing thymocytes and that there is a distinct cytokine signaling requirement in CD4/CD8 lineage differentiation. In particular, we show that CD8 cell differentiation is dependent on additional cues by cytokines such as interleukin-7 (IL-7). Using conditional deletion of immediate downstream signaling molecules of the IL-7 receptor, we demonstrate that IL-7-induced cytokine signals are required for CD8 lineage choice and for the differentiation into mature CD8+ cytotoxic T cells in vivo. Our data establish a previously unappreciated role for in vivo IL-7 and other gamma c-cytokines in CD8 lineage commitment of immature thymocytes, which is consistent with the Okinetic signaling model' of T cell lineage choice.