The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online 28 March 2005 doi:10.1084/jem.20041059
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 7, 1045-1051
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BRIEF DEFINITIVE REPORT

 A role for CCR4 in development of mature circulating cutaneous T helper memory cell populations

Espen S. Baekkevold1,2,3, Marc-André Wurbel1,2, Pia Kivisäkk1,2, Clare M. Wain1,2, Christine A. Power4, Guttorm Haraldsen3, and James J. Campbell1,2

1 Children's Hospital, Joint Program in Transfusion Medicine
2 Department of Pathology, Harvard Medical School, Boston, MA 02115
3 Institute of Pathology, University of Oslo, Rikshospitalet University Hospital, Oslo N-0027, Norway
4 Serono Pharmaceutical Research Institute, Geneva CH 1228, Switzerland

CORRESPONDENCE James J. Campbell: james.campbell{at}childrens.harvard.edu

Expression of the chemokine receptor CCR4 is strongly associated with trafficking of specialized cutaneous memory T helper (Th) lymphocytes to the skin. However, it is unknown whether CCR4 itself participates in the development of cutaneous Th populations. We have addressed this issue via competitive bone marrow (BM) reconstitution assays; equal numbers of BM cells from CCR4+/+ and CCR4–/– donors were allowed to develop side-by-side within RAG-1–/– hosts. Cells from both donor types developed equally well into B cells, naive CD8 T cells, naive CD4 T cells, interferon-{gamma}+ Th1 cells, and interleukin-4+ Th2 cells. In marked contrast, circulating cutaneous memory Th cells (i.e., E-selectin ligand+ [E-lig+]) were more than fourfold more likely to be derived from CCR4+/+ donors than from CCR4–/– donors. Most of this effect resides within the CD103+ subset of the E-lig+ Th population, in which donor CCR4+/+ cells can outnumber CCR4–/– cells by >12-fold. No similar effect was observed for {alpha}4ß7+ intestinal memory Th cells or CD103+/E-lig– Th cells. We conclude that CCR4 expression provides a competitive advantage to cutaneous Th cells, either by participating in their development from naive Th cells, or by preferentially maintaining them within the memory population over time.

E.S. Baekkevold and M.-A. Wurbel contributed equally to this work.


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