Unaltered graft survival and intragraft lymphocytes infiltration in the cardiac allograft of Cxcr3-/- mouse recipients

J. Kwun, S. M. Hazinedaroglu, E. Schadde, H. A. Kayaoglu, J. Fechner, H. Z. Hu, D. Roenneburg, J. Torrealba, L. Shiao, X. Hong, R. Peng, J. W. Szewczyk, K. A. Sullivan, J. DeMartino, S. J. Knechtle

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27 Scopus citations

Abstract

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3-/- mice. Interestingly, in our hands, neither of the independently derived Cxcr3-/- lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-γ production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3-/- recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.

Original languageEnglish (US)
Pages (from-to)1593-1603
Number of pages11
JournalAmerican Journal of Transplantation
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2008

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Keywords

  • Acute rejection
  • Cardiac allograft
  • Cell trafficking
  • Mouse
  • T-cell graft infiltration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Kwun, J., Hazinedaroglu, S. M., Schadde, E., Kayaoglu, H. A., Fechner, J., Hu, H. Z., Roenneburg, D., Torrealba, J., Shiao, L., Hong, X., Peng, R., Szewczyk, J. W., Sullivan, K. A., DeMartino, J., & Knechtle, S. J. (2008). Unaltered graft survival and intragraft lymphocytes infiltration in the cardiac allograft of Cxcr3-/- mouse recipients. American Journal of Transplantation, 8(8), 1593-1603. https://doi.org/10.1111/j.1600-6143.2008.02250.x