Synthesis of the CC-chemokines MIP-1alpha, MIP-1beta, and RANTES is associated with a type 1 immune response.

Abstract

Lymphocytes regulate the immune response by secreting cytokines that control the activity and function of effector cells. Chemokine subsets are ideal candidates for recruitment of specific effector cells to inflammatory sites or to other lesions because of their selective chemoattractant activities. Given the Th1-Th2 model of immune regulation and the particular role of leukocyte recruitment for the outcome of the response, we analyzed whether a subset of human chemokines is associated with a specific type of immune response. Therefore, we have analyzed the human T cell response to Ags prepared from Yersinia enterocolitica and Ascaris suum with respect to cytokine mRNA-synthesis and secretion. For the Gram-negative bacterium Y. enterocolitica, induction of a type 1 response is indicated by IL-2 and IFN-gamma production, and for the nematode A. suum, a type 2 response is based on IL-4 and IL-5 production. Interestingly, expression of three CC-chemokines (i.e., MIP-1alpha, MIP-1beta, and RANTES) correlated with the type 1 response induced by Y. enterocolitica Ag. Chemokine secretion is not restricted to T lymphocytes; therefore, synthesis of MIP-1alpha, MIP-1beta, and RANTES was also characterized in human T cell clones that display a cytokine pattern indicative of the Th2, Th0, or Th1 phenotype. Again CC-chemokine secretion correlated with the Th1-like phenotype. In six analyzed IL-2- and IFN-gamma- secreting Th1 clones and in two Th0 clones, MIP-1alpha, MIP-1beta, and RANTES were detected, while none or only minimal secretion of these CC-chemokines was observed in three IL-4- and IL-5-producing Th2 cell clones.