Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role in the pathogenesis of chronic GVHD

Croudace, Joanne, Inman, C., Abbotts, B., Nagra, S., Nunnick, J., Mahendra, P., Craddock, C., Malladi, R. and Moss, P. (2012) Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role in the pathogenesis of chronic GVHD. Blood, 120 (20). pp. 4246-4255. ISSN Print: 0006-4971 Online: 1528-0020

Abstract

Chemokines regulate the migration of hemopoietic cells and play an important role in the pathogenesis of many immune-mediated diseases. Intradermal recruitment of CD8+ T cells by CXCL10 is a central feature of the pathogenesis of cutaneous acute GVHD (aGVHD), but very little is known about the pathogenesis of chronic GVHD (cGVHD). Serum concentrations of the 3 CXCR3-binding chemokines, CXCL9, CXCL10, and CXCL11, were found to be markedly increased in patients with active cGVHD of the skin (n = 8). An 80% decrease in CD4+ cells expressing CXCR3 was seen in the blood of these patients (n = 5), whereas CD4+ cells were increased in tissue biopsies and were clustered around the central arterioles of the dermis. The well-documented increase in expression of CXCL10 in aGVHD therefore diversifies in cGVHD to include additional members of the CXCR3-binding family and leads to preferential recruitment of CD4+ T cells. These observations reveal a central role for chemokine-mediated recruitment of CXCR3+ T cells in cGVHD.

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