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 language | English (US) |
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Pages (from-to) | 1593-1603 |
Number of pages | 11 |
Journal | American Journal of Transplantation |
Volume | 8 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2008 |
Keywords
- Acute rejection
- Cardiac allograft
- Cell trafficking
- Mouse
- T-cell graft infiltration
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)