Role of CXCR3-induced donor T-cell migration in acute GVHD

Exp Hematol. 2003 Oct;31(10):897-902. doi: 10.1016/s0301-472x(03)00198-x.


Objective: The chemokine receptor CXCR3 has an important role in the migration of effector T cells. To investigate the role of CXCR3 on donor cells in acute graft vs host disease (GVHD) we used a well-defined experimental bone marrow transplantation (BMT) model where acute GVHD is mediated by donor CD8(+) T cells against minor histocompatibility antigens. METHODS; Lethally irradiated C3H.SW recipients were transplanted from either wild-type B6 or CXCR3(-/-) B6 donors. Donor T-cell expansion was analyzed in the spleen and small intestine of recipients by FACS. Donor T-cell function was analyzed by cytokine secretion. The severity of acute GVHD was assessed by histopathological analysis of intestine and liver, GVHD clinical scores, and survival after BMT.

Results: Significantly higher numbers of donor CD8(+) CXCR3(-/-) T cells were found in the spleen on days +7 and +14 compared to donor wild-type T cells. By contrast, the number of CD8(+) T cells in the small bowel of BMT recipients from CXCR3(-/-) donors was sevenfold lower than from wild-type donors. Systemic concentrations of INF-gamma and TNF-alpha were equivalent between groups. Animals that received CXCR3(-/-) donor T cells demonstrated diminished GI tract and liver damage and showed improved survival after BMT compared to recipients of wild-type donor cells (43% vs 0%, p<0.001).

Conclusion: The migration of donor CD8(+) T cells to GVHD target organs such as the intestine depends on the expression of CXCR3 and contributes significantly to GVHD damage and overall mortality.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Bone Marrow Transplantation
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Movement
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / mortality
  • Interferon-gamma / analysis
  • Liver / pathology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, CXCR3
  • Receptors, Chemokine / physiology*
  • Tissue Donors
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / analysis


  • Cxcr3 protein, mouse
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma