Cutting edge: Hierarchy of chemokine receptor and TCR signals regulating Tcell migration and proliferation

Chemokines play an important role in establishing the distribution of lymph ocyte subpopulations in primary and secondary lymphoid tissues and in the r ecruitment of leukocytes to sites of inflammation. However, the potential o f chemokines to down-regulate immune responses has not been demonstrated. W e now show that certain chemokine gradients have the potential to suppress T cell activation by preventing formation of the immunological synapse, the specialized cell-cell junction that forms before a T cell can be fully act ivated. Our data reveals an immunosuppressive potential of chemokines engag ing the CXCR3 and CCR7 receptors, but not the CXCR4, CCR2, CCR4, or CCR5 re ceptors, These results suggest a novel mechanism for T cell ignorance of ag onist MHC-peptide complexes based on dominant chemokine gradients.