TCR activation inhibits chemotaxis toward stromal cell-derived factor-1: Evidence for reciprocal regulation between CXCR4 and the TCR

Stromal cell-derived factor-1 (SDF-1), a C-X-C family chemokine, is a poten t T lymphocyte chemoattractant. We investigated the effects of T cell activ ation on the chemotactic response to SDF-1, Anti-CD3 Ab stimulation of eith er Jurkat T cells or murine peripheral CD4(+) T lymphocytes produced a dram atic inhibition of SDF-1-induced chemotaxis, In contrast, the SDF-1 respons es of Jurkat clones with deficiencies in key TCR signaling components (Lck, CD45, and TCR-beta), were only marginally reduced by anti-CD3 stimulation. Similar to PMA treatment, which abolished both CXCR4 receptor expression a nd the chemotactic response of Jurkat cells to SDF-1, anti-CD3 Ab treatment reduced cell surface expression of CXCR4 to 65% of the control value, an e ffect that was blocked by protein kinase C inhibitors. Our data suggest tha t initial T cell activation events inhibit the response of Jurkat T cells t o CXCR4 stimulation, In contrast, SDF-1 treatment resulted in a reduction o f tyrosine phosphorylation of the TCR downstream effecters, ZAP-70, SLP-76, and LAT (linker for activation of T cells), suggesting that this chemokine potentially regulates the threshold for T cell activation.