The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes

CC Bleul, L Wu, JA Hoxie… - Proceedings of the …, 1997 - National Acad Sciences
CC Bleul, L Wu, JA Hoxie, TA Springer, CR Mackay
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
The chemokine receptors CXCR4 and CCR5 function as coreceptors for HIV-1 entry into
CD4+ cells. During the early stages of HIV infection, viral isolates tend to use CCR5 for viral
entry, while later isolates tend to use CXCR4. The pattern of expression of these chemokine
receptors on T cell subsets and their regulation has important implications for AIDS
pathogenesis and lymphocyte recirculation. A mAb to CXCR4, 12G5, showed partial
inhibition of chemotaxis and calcium influx induced by SDF-1, the natural ligand of CXCR4 …
The chemokine receptors CXCR4 and CCR5 function as coreceptors for HIV-1 entry into CD4+ cells. During the early stages of HIV infection, viral isolates tend to use CCR5 for viral entry, while later isolates tend to use CXCR4. The pattern of expression of these chemokine receptors on T cell subsets and their regulation has important implications for AIDS pathogenesis and lymphocyte recirculation. A mAb to CXCR4, 12G5, showed partial inhibition of chemotaxis and calcium influx induced by SDF-1, the natural ligand of CXCR4. 12G5 stained predominantly the naive, unactivated CD26low CD45RA+ CD45R0 T lymphocyte subset of peripheral blood lymphocytes. In contrast, a mAb specific for CCR5, 5C7, stained CD26high CD45RAlow CD45R0+ T lymphocytes, a subset thought to represent previously activated/memory cells. CXCR4 expression was rapidly up-regulated on peripheral blood mononuclear cells during phytohemagglutinin stimulation and interleukin 2 priming, and responsiveness to SDF-1 increased simultaneously. CCR5 expression, however, showed only a gradual increase over 12 days of culture with interleukin 2, while T cell activation with phytohemagglutinin was ineffective. Taken together, the data suggest distinct functions for the two receptors and their ligands in the migration of lymphocyte subsets through lymphoid and nonlymphoid tissues. Furthermore, the largely reciprocal expression of CXCR4 and CCR5 among peripheral blood T cells implies distinct susceptibility of T cell subsets to viral entry by T cell line-tropic versus macrophage-tropic strains during the course of HIV infection.
National Acad Sciences