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

Helper T cells are classified into T(h)1 and T(h)2 subsets based on their p rofiles of cytokine production. T(h)1 cells are involved in cell-mediated i mmunity, whereas T(h)2 cells induce humoral responses. Selective recruitmen t of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokin e 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-deriv ed chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on similar to 20% of adult peripheral blood effector/memory C D4(+) T cells. T cells attracted by TARC and MDC generated cell lines predo minantly 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 polarize d in vitro, T(h)2-type cells selectively expressed CCR4 and vigorously migr ated toward TARC and MDC. Taken together, CCR4 is selectively expressed on T(h)2-type T cells and antigen-presenting cells may recruit Th2 cells expre ssing CCR4 by producing TARC and MDC in T(h)2-dominant conditions.