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

JE Croudace, CF Inman, BE Abbotts… - Blood, The Journal …, 2012 - ashpublications.org
JE Croudace, CF Inman, BE Abbotts, S Nagra, J Nunnick, P Mahendra, C Craddock
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
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 …
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.
ashpublications.org