Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes.
The responses of lymphocytes to six CC chemokines--MCP-1, MCP-2, MCP-3, MIP-1 alpha, MIP-1 beta, and RANTES--were studied using cloned human CD4+ and CD8+ T cells. All CC chemokines tested induced migration of both types of lymphocytes, whereas two CXC chemokines used as controls, IL-8 and IP-10, were inactive. The monocyte chemotactic proteins (MCP-1, MCP-2, and MCP-3) showed a typically bimodal concentration dependence, and were considerably more effective than MIP-1 alpha, MIP-1 beta, or RANTES. All CC chemokines also induced a rapid and transient rise in cytosolic free Ca2+ in either type of T cell. The rise was prevented by Bordetella pertussis toxin treatment, indicating that G-protein-coupled receptors are involved in signaling. It was most pronounced with MCP-1 and MCP-3, which is in agreement with the efficacy of these chemokines as chemoattractants. The responses to MCP-2, MIP-1 alpha, MIP-1 beta, and RANTES were weaker, and no changes were obtained on stimulation with IL-8 or IP-10. Freshly isolated human blood lymphocytes were also tested, but neither migration nor Ca2+ changes were observed. Low numbers of high-affinity receptors for MCP-1 were found on CD4+ and CD8+ cells ( < 900 per cell, Kd < 1 nM), and desensitization experiments showed that MCP-1, MCP-2, and MCP-3 share receptors. Owing to their superior effectiveness on CD4+ and CD8+ T cells, the monocyte chemotactic proteins could play a major role in the recruitment of activated T lymphocytes.
Loetscher
P
P
Theodor-Kocher Institute, University of Bern, Switzerland.
Seitz
M
M
Clark-Lewis
I
I
Baggiolini
M
M
Moser
B
B
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D002999:Clone Cells; D016207:Cytokines; D006801:Humans; D018945:Monocyte Chemoattractant Proteins; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
C515450:CCL7 protein, human; C515453:CCL8 protein, human; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D002630:Chemotactic Factors; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D002118:Calcium