Chemokines, lymphocytes, and HIV

Abstract

Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. 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 relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-γ and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3α, and STRL22 has been renamed CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit.

Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1- Infected Individuals

“…MIP-3α is the only chemokine that has high specificity for the chemokine receptor, CCR6 [10-13], which is expressed on several human cell types implicated in HIV infection, including immature dendritic cells (iDCs) [14], effector/memory CD8 + and CD4 + T cells [15,16], and interleukin-17 (IL-17) producing T cells (TH 17 ).…”

The role of chemokines in vertebrate physiology and disease: a concise review

“…CD4 is considered the primary receptor for HIV, where gp 120 and gp 41 (envelope proteins) mediate virus binding to the target cell membrane followed by consequent interaction with chemokine receptors CCR3 and 5 CCR2B or CXCR4 leading to merging of the host cell membrane and HIV membrane [63][64][65][66][67][68][69][70][71][72]. Other chemokines, CCR2, 3, 8 and 9, STRL33, Gpr15, Gpr1, APJ, ChemR23 and CX3CR1, are also used by HIV for host cell entry during in vitro infection [64,[73][74][75][76].…”