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

The chemokine receptors CXCR4 and CCR5 function as coreceptors for HIV-1 entry into CD4 1 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 recep- tors on T cell subsets and their regulation has important implications for AIDS pathogenesis and lymphocyte recircu- lation. 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 CD26 low CD45RA 1 CD45R0 2 T lymphocyte sub- set of peripheral blood lymphocytes. In contrast, a mAb specific for CCR5, 5C7, stained CD26 high CD45RA low CD45R0 1 T lymphocytes, a subset thought to represent pre- viously activatedymemory cells. CXCR4 expression was rap- idly up-regulated on peripheral blood mononuclear cells dur- ing phytohemagglutinin stimulation and interleukin 2 prim- ing, 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. Further- more, 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-tropicstrainsduringthecourseofHIVinfection.