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

Blood. 2012 Nov 15;120(20):4246-55. doi: 10.1182/blood-2012-02-413260. Epub 2012 Sep 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Arterioles / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / physiology*
  • Chemokine CXCL11 / blood
  • Chemokine CXCL11 / physiology*
  • Chemokine CXCL9 / blood
  • Chemokine CXCL9 / physiology*
  • Chemotaxis, Leukocyte
  • Dermis / blood supply
  • Dermis / immunology
  • Dermis / pathology
  • Disease Progression
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Hematologic Neoplasms / surgery
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Receptors, CXCR3 / physiology*
  • Transplantation Conditioning


  • CXCL10 protein, human
  • CXCL11 protein, human
  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Receptors, CXCR3