CXCL10-CXCR3 Interactions Play an Important Role in the Pathogenesis of Acute Graft-versus-host Disease in the Skin Following Allogeneic Stem-cell Transplantation

Acute graft-versus-host disease (aGVHD) remains a serious complication following allogeneic stem-cell transplantation (SCT), and is mediated by infiltration of alloreactive donor T cells into recipient tissue. Chemokines and their receptors play a central role in controlling the recruitment of T cells into discrete tissue sites, and determine the clinical features of GVHD in murine models. In this study, we have analyzed the serum concentration of molecules that control leukocyte migration in serial samples from 34 patients following allogeneic SCT. The chemokine CXCL10 (IP-10) was significantly elevated (> 2-fold) in serum at the time of aGVHD. Because the ligand for CXCL10 is CXCR3, the number of CXCR3(+) T cells was determined in peripheral blood, but was not increased during episodes of GVHD. To investigate the role of chemokines in the recruitment of T cells to the anatomic site of GVHD, skin biopsies were stained for CXCL10 and CXCR3 expression. CXCL10 expression was observed in the basal keratinocytes of the epidermis in patients with GVHD together with positive staining for CXCR3 on cells in dermal infiltrates. These findings indicate that CXCL10 plays a central role in the pathogenesis of skin aGVHD by the recruitment of CXCR3(+) T cells to the sites of inflammation.