Blood, 1 July 2005, Vol. 106, No. 1, pp. 18-26.
Prepublished online as a Blood First Edition Paper on March 17, 2005; DOI 10.1182/blood-2004-08-2996.
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CHEMOKINES
CCR6 regulates CD4+ T-cell–mediated acute graft-versus-host disease responses
Rosa Varona,
Vanesa Cadenas,
Lucio Gómez,
Carlos Martínez-A, and
Gabriel Márquez
From the Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
We studied the role of chemokine receptor CCR6 in acute graft-versus-host disease (GvHD), a pathology in which activated, host antigen-specific donor T cells selectively damage tissues such as skin, liver, and gut. GvHD incidence was reduced in major histocompatibility complex (MHC) class II–mismatched recipients of CD4+ T cells from CCR6-deficient donors. In MHC-matched/minor histocompatibility antigen–mismatched recipients of CD4+CD45RBhigh T cells from CCR6-deficient donors, infiltration of CD45+ and CD4+ cells to skin and gut, as well as lesion onset, were significantly delayed, and pathologic symptoms were milder. Consistent with this, in skin and gut of recipients of naive T cells from CCR6-deficient donors we observed lower levels of interferon  (IFN-), interleukin 10 (IL-10), and the chemokines that control activated T-cell homing. We suggest a role for CCR6 in recruiting alloreactive CD4+ T cells to target tissues and identify CCR6 as a potential therapeutic target for GvHD.
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