Unaltered Graft Survival and Intragraft Lymphocytes Infiltration in the Cardiac Allograft of Cxcr3−/- Mouse Recipients |
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Authors: | 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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Institution: | Division of Transplantation,Department of Surgery, University of Wisconsin-Madison;Department of Pathology, Clinical Science Center, University of Wisconsin, Madison, WI;Departments of Laboratory Animal Resources;Medicinal Chemistry;Immunology, Merck Research Laboratories, Merck, Rahway, NJ |
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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. |
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Keywords: | Acute rejection cardiac allograft cell trafficking mouse T-cell graft infiltration |
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