Chemokine regulation of T cell cytokine production

Chemokines are a family of small molecular weight cytokines that induce the chemotaxis and chemokinesis of leukocytes. These molecules are Ikjands for seven-transmembrane, G-protein-linked receptors and are known to activate integrins on the surface of leukocytes and other cells as well as induce a signaling cascade in human T cells. Therefore, they play a significant role in the migration of leukocytes from blood into tissue during inflammatory processes. We wanted to determine if chemokines played a role in either the differentiation of T cell phenotypes or simply potentiated T cell cytokine production without affecting differentiation. Bulk lymph node cells from peptide antigen-primed mice were incubated in the presence of either macrophage inflammatory protem-1 a (MIP-1a), monocyte chemotactic protein-1 (MCP-1), or control plus specific antigen at the initiation of the culture period. Cells incubated in the presence of MIP-1a showed enhanced IFN-y production compared to cells from control treated cultures. In contrast, cells incubated in the presence of MCP-1 showed enhanced IL-4 production. Similar results were obtained when purified T cells were stimulated with antiCD3 instead of specific antigen. Splenic T cells from DO11.10 OVA TCR transgenic mice were used as a source of naive ThO cells. These cells were either stimulated with specific peptide or anti-donotypic mAb in the presence of MIP-1a, MCP-1 or control. MIP-1a increased IFN-y and concomitantly decreased IL-4 production whereas MCP-1 decreased IFN-γ and concomitantly increased IL-4 production. These results suggest a wider role for chemokines in an immune response in addition to reaulatjnq leukocyte trafficking.