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The FASEB Journal, Vol 8, 1055-1060, Copyright © 1994 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes

P Loetscher, M Seitz, I Clark-Lewis, M Baggiolini and B Moser
Theodor-Kocher Institute, University of Bern, Switzerland.

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.


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