CHEMOKINES, LYMPHOCYTES, AND HIV

Chemokines are members of a family of more than 30 human cytokines who se best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and tr afficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly unders tood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the rela tionships between chemokines and lymphocytes. My laboratory has charac terized Mig and Crg-2/IP-10, chemokines that are induced by IFN-gamma and that specifically target lymphocytes, particularly activated T cel ls. We have demonstrated that the genes for these chemokines are widel y expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression dif fered, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted i n the cloning of STRL22 and STRL33. We and others have shown that STRL 22 is a receptor for the CC chemokine MIP-3 alpha, and STRL22 has been renamed CCR6. Although STRL33 remains an orphan receptor, we have sho wn that it can function as a co-receptor for HIV-1 envelope glycoprote ins, and that it is active with a broader range of HIV-1 envelope glyc oproteins than the major co-receptors described to date. The ability o f STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block ot her specific co-receptors. We presume that investigations into the rol es of chemokines and their receptors in lymphocyte biology will provid e information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benef it.