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

Abstract

The responses of lymphocytes to six CC chemokines–MCP‐1, MCP‐2, MCP‐3, MIP‐1α, MIP‐1β, 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‐1α, MIP‐10, or RANTES. All CC chemokines also induced a rapid and transient rise in cytosolic free Ca 2+ 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‐1α, MIP‐1β, 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 Ca 2+ changes were observed. Low numbers of high‐affinity receptors for MCP‐1 were found on CD4 + and CD8+ cells (<900 per cell, K d <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., Seitz, M., Clark‐Lewis, I., Baggiolini, M., Moser, B. Monocyte chemotactic proteins MCP‐1, MCP‐2, and MCP‐3 are major attractants for human CD4 + and CD8 + T lymphocytes. FASEB J. 8: 1055‐1060; 1994.