Besides chemotaxis, C-X-C and C-C chemokines function as mediators in T-cell activation and in many lymphocyte biological responses. Detailed information about downstream signaling pathways is necessary to understand the role of chemokines in normal physiology and inflammation. We have built several focused cDNA chips containing approximately 3000 known human genes that are expressed and secreted by a variety of cell types including lymphoid cells and participate in cell growth, signal transduction, effector functions, CD molecules, metabolism and apoptosis. Additional studies using 44K oligonucleotide arrays are underway examining the ability of various chemokines, HIV-1 viral isolates, and gp120 proteins to directly induce gene expression in young and old human T lymphocytes. We are currently verifying and characterizing several gene families that are highly expressed in T cells after migration in response to or simply stimulation with SDF-1, MIP-3beta, gp120 and HIV-1 virus. A greater understanding of the transcriptional signals differentially induced by the ligation of various chemokine receptors may provide a means to dissect the pathways by which these chemoattractants induce cell migration and activation as well as any host transcriptional signals important in HIV entry and replication.
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