Differential expression of binding sites for chemokine RANTES on human T lymphocytes.
The C-C chemokine RANTES, a T lymphocyte chemoattractant, is considered an important mediator of inflammation, allergy, and host defense against HIV-1 infection. In this study, we investigated the modulation of binding of RANTES to T lymphocytes. Human peripheral blood CD3+ T cells, when freshly isolated from buffy-coat blood, expressed a considerable number of high-affinity binding sites for RANTES. These cells also showed significant chemotactic migration in response to RANTES in vitro. 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. Scatchard analyses indicated that the number of binding sites for RANTES increased about threefold by 15 h without any change in the affinity. The increase in RANTES binding was no longer detected by 24 h. This increase in the specific binding was mainly attributable to CD4+ T cells and was not associated with increased chemotactic activity of these cells 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, when T cells were incubated with interleukin-2 (IL-2) for 1 week, the specific binding for all three C-C chemokines, RANTES, MIP-1 alpha, and MCP-3 was markedly increased in comparison to cells cultured in the absence of IL-2. These results suggest that the expression of binding sites on T cells for RANTES is differentially modulated, indicating the existence of novel receptors for RANTES that do not bind MIP-1 alpha.
Utsunomiya
I
I
Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
Tani
K
K
Gong
W
W
Oppenheim
J J
JJ
Wang
J M
JM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism*; D054410:Chemokine CCL7; D016207:Cytokines; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C515450:CCL7 protein, human; D017252:CD3 Complex; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D016207:Cytokines; D007457:Iodine Radioisotopes; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins