DIFFERENTIAL EXPRESSION OF BINDING-SITES FOR CHEMOKINE RANTES ON HUMAN T-LYMPHOCYTES

The C-C chemokine RANTES, a T lymphocyte chemoattractant, is considere d an important mediator of inflammation, allergy, and host defense aga inst HIV-1 infection. In this study, we investigated the modulation of binding of RANTES to T lymphocytes. Human peripheral blood CD3(+) T c ells, when freshly isolated from buffy-coat blood, expressed a conside rable number of high-affinity binding sites for RANTES. These cells al so showed significant chemotactic migration in response to RANTES in v itro. After 6-15 h incubation at 37 degrees C, the binding of RANTES, but not of macrophage inflammatory protein-1 alpha (MIP-1 alpha) or of monocyte chemotactic protein-3 (MCP-3), consistently increased. Scatc hard analyses indicated that the number of binding sites for RANTES in creased about threefold by 15 h without any change in the affinity. Th e increase in RANTES binding was no longer detected by 24 h. This incr ease in the specific binding was mainly attributable to CD4(+) T cells and was not associated with increased chemotactic activity of these c ells in response to RANTES. Incubation with anti-CD3 antibody for 15 h markedly reduced the binding capability of T cells for RANTES and was associated with decreased chemotactic activity. On the other hand, wh en T cells were incubated with interleukin-2 (IL-2) for 1 week, the sp ecific binding for all three C-C chemokines, RANTES, MIP-1 alpha, and MCP-3 was markedly increased in comparison to cells cultured in the ab sence of IL-2. These results suggest that the expression of binding si tes on T cells for RANTES is differentially modulated, indicating the existence of novel receptors for RANTES that do not bind MIP-1 alpha.