Selective recruitment of CCR4-bearing Th2 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 Th1 and Th2 subsets based on their profiles of cytokine production. Th1 cells are involved in cell-mediated immunity, whereas Th2 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 approximately 20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing Th2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to Th2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, Th2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on Th2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in Th2-dominant conditions.

IL-13-Induced Chemokine Responses in the Lung: Role of CCR2 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling

“…When viewed in combination, these studies provide impressive insights into the pathogenesis of the complex IL-13-induced inflammatory and remodeling responses in these animals. Specifically, this complex chemokine response may contribute to the eosinophil-, macrophage/monocyte-, and lymphocyte-rich inflammation in these mice because MCPs, eotaxin, eotaxin-2, MIP-1␣, and MDC stimulate eosinophil chemotaxis; MCPs, MIP-1␣, MIP-1␤, C10, MDC, and TARC stimulate monocyte chemotaxis and MDC, TARC, eotaxin, and eotaxin-2 are vigorous and selective stimulators of T cell chemotaxis (17,26,(37)(38)(39)(40)(41)(42)(43). In addition, FIGURE 7.…”

Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity

“…36 MDC is a potent chemoattractant for DC, NK cells, Th2 and Tc2 subsets of T cells. 1,2,6 The functional receptor for MDC is the CC chemokine receptor 4 (CCR4), which is preferentially expressed on blood T cells, particularly CD4 + T cells of the Th2 phenotype. 2 MDC is thought to…”

“…2,6 In normal human tissues, MDC and its receptor CCR4 are expressed almost exclusively in thymus, where it is a chemoattractant for CD3 + CD4 + and CD8 (low) thymocytes. 37 In this study, we have confirmed our hypothesis that adenovirus-mediated intratumoral MDC gene transfer could suppress the growth of 3LL tumors, increase survival of the tumor-bearing mice, and induced tumor-specific cytotoxic T cell response.…”

“…5 It was reported that T cells attracted by MDC gene-transfected cell lines could predominantly produce Th2-type cytokines, such as IL-4. 2,6 Previous data have shown that the growth of IL-4 gene-transfected tumors in vivo was suppressed in a rather reproducible fashion. 7,8 It has been reported that…”

Chemokines: attractive mediators of the immune response

“…A cellular or T helper (Th)1 response is associated with interferon-␥ production and macrophage activation, whereas a humoral or Th2 response is characterized by IL-4 and IL-5 production, B cell help and an antibody response. Chemokine receptors are markers for T helper subsets: CCR5 and CXCR3 are markers for Th1 cells [20,21], while CCR2 and CCR4 are expressed by Th2 cells [22,23]. Furthermore, ligands for CCR5 (CCL3, CCL4, and CCL5) have been shown to be chemotactic for Th1 and not Th2 cells [24].…”