Unaltered Graft Survival and Intragraft Lymphocytes Infiltration in the Cardiac Allograft of Cxcr3−/‐ Mouse Recipients

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. Our study, targeting the CXCR3 chemokine receptor on human CXCR3 knock in mice and two additional CXCR3 deficient mouse strains, found a limited/marginal role of CXCR3 on intragraft lymphocyte infiltration and preventing acute rejection in full MHC mismatched cardiac allografts. See also editorial by Halloran and Fairchild in this issue on page 1578.