CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking

Abstract

The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific T_H lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin–dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human T_Hpopulations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell–attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of T_H subsets. We find CCR10 expressed by only a minority (approximately 30%) of blood-borne, skin-homing (CLA⁺/CCR4⁺) T_H cells. However, essentially all members of the relatively small “effector” (CLA⁺/CCR4⁺/CD27⁻/CCR7⁻) skin-homing T_H population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10% express CCR10. This suggests for the 2 models of T_H skin homing studied here that CCR10⁺ T_H cells have no advantage over other CLA⁺/CCR4⁺ T_H cells in homing to cutaneous sites. We conclude that the skin-homing T_Hcompartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of T_H cells in the models studied here. CCR10 may instead play a role in the movement of specialized “effector” cutaneous T_H cells to and/or within epidermal microenvironments.