THE CHEMOKINE RECEPTORS CXCR3 AND CCR5 MARK SUBSETS OF T-CELLS ASSOCIATED WITH CERTAIN INFLAMMATORY REACTIONS

T cells infiltrating inflammatory sites are usually of the activated/m emory type. The precise mechanism for the positioning of these cells w ithin tissues is unclear, Adhesion molecules certainly play a role; ho wever, the intricate control of cell migration appears to be mediated bf numerous chemokines and their receptors, Particularly important che mokines for activated/memory T cells are the CXCR3 ligands IP-10 and M ig and the CCR5 ligands RANTES, macrophage inflammatory protein-let, a nd macrophage inflammatory protein-1 beta. We raised anti-CXCR3 mAbs a nd were able to detect high levels of CXCR3 expression on activated T cells, Surprisingly, a proportion of circulating blood T cells, B cell s, and natural killer cells also expressed CXCR3, CCR5 showed a simila r expression pattern as CXCR3, but was Expressed on fewer circulating T cells, flood T cells expressing CXCR3 (and CCR5) were mostly CD45RO( +), and generally expressed high levels of pi integrins, This phenotyp e resembled that of T cells infiltrating inflammatory lesions, Immunos taining of T cells in rheumatoid arthritis synovial fluid confirmed th at virtually all such T cells expressed CXCR3 and similar to 80% expre ssed CCR5, representing high enrichment over levels of CXCR3(+) and CC R5(+) T cells in blood, 35 and 15%, respectively, Analysis by immunohi stochemistry of various inflamed tissues gave comparable findings in t hat virtually all T cells within the lesions expressed CXCR3, particul arly in perivascular regions, whereas far fewer T cells within normal lymph nodes expressed CXCR3 or CCR5, These results demonstrate that th e chemokine receptor CXCR3 and CCR5 are markers for T cells associated with certain inflammatory reactions, particularly TH-1 type reactions , Moreover, CXCR3 and CCR5 appear to identify subsets of T cells in bl ood with a predilection for homing to these sites.