LYMPHOCYTE-SPECIFIC CHEMOKINE RECEPTOR CXCR3 - REGULATION, CHEMOKINE BINDING AND GENE LOCALIZATION

Expression of CXCR3, the receptor for the CXC chemokines IFN-gamma-ind ucible 10-kDa protein (IP10) and monokine induced by IFN-gamma (Mig), in human T lymphocytes and their responses to IP10 and Mig were analyz ed. About 40 % of vesting T lymphocytes (and low numbers of B cells an d natural killer cells) stained positive for CXCR3 but these cells did not express CXCR3 transcripts and did not respond to these chemokines . However, treatment with IL-2 with or without addition of phytohemagg lutinin for 10 or more days resulted in cultures of fully responsive, CXCR3-positive T lymphocytes. Treatment with anti-CD3 antibodies in th e presence or absence of soluble anti-CD28 antibodies was inhibitory. Addition of chondroitin sulfate C to CXCR3-expressing murine pre-B cel ls allowed the determination of high-affinity binding for Mig and IP10 with K-d of 0.9-1.2 nM and 0.2-0.3 nM, respectively, and 1.3 x 10(4) binding sites per cell. The gene for CXCR3 was localized on human chro mosome Xq13 which is in clear contrast to all other chemokine receptor genes, suggesting unique function(s) for this receptor and its ligand s that may lie beyond their established role in T cell-dependent immun ity.