Selective recruitment of CCR4-bearing T(h)2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine

Abstract

Helper T cells are classified into T(h)1 and T(h)2 subsets based on their profiles of cytokine production. T(h)1 cells are involved in cell-mediated immunity, whereas T(h)2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4. The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on ~20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing T(h)2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to T(h)2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, T(h)2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on T(h)2-type T cells and antigen-presenting cells may recruit T(h)2 cells expressing CCR4 by producing TARC and MDC in T(h)2-dominant conditions.