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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2348.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1677-1682
CHEMOKINES
CCR4 versus CCR10 in human cutaneous TH lymphocyte
trafficking
Dulce Soler,
Tricia L. Humphreys,
Stanley M. Spinola, and
James J. Campbell
From Millennium Pharmaceuticals, Inflammation
Department, Cambridge, MA; the Department of Medicine, Indiana
University School of Medicine, Indianapolis, IN; the Departments of
Microbiology and Immunology, and Pathology and Laboratory Medicine,
Indiana University School of Medicine, Indianapolis, IN; the Department
of Pathology, Harvard Medical School, Boston, MA; and the Joint Program
in Transfusion Medicine, Children's Hospital, Boston, MA.
The chemokine receptors (CCRs) CCR4 and CCR10, and the
cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH 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 TH
populations. 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 TH subsets. We find CCR10 expressed by only a
minority (approximately 30%) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However,
essentially all members of the relatively small "effector"
(CLA+/CCR4+/CD27 /CCR7 )
skin-homing TH 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 TH skin homing studied here
that CCR10+ TH cells have no advantage over
other CLA+/CCR4+ TH cells in homing
to cutaneous sites. We conclude that the skin-homing TH
compartment 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 TH cells in the models studied here.
CCR10 may instead play a role in the movement of specialized
"effector" cutaneous TH cells to and/or within
epidermal microenvironments.

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