CXCL9 promotes development of IFN‐γ‐producing alloreactive CD8 T cells but is not a dominant factor in directing graft infiltration following heterotopic cardiac allografting

Abstract

Factors influencing T cell polarization during priming to cardiac allografts are poorly understood. We investigated the role of CXCL9 (MIG) in priming CD8 T cells to allografts and whether MIG recruits primed CD8 T cells to the graft. To measure MIG in the priming site, DCs and B cells were purified from B6 recipients of MHC‐mismatched A/J grafts on d 7 post‐transplant (pTx), and qRT‐PCR was performed. In allograft recipients, DCs produced 50x greater MIG mRNA than B cells. To monitor effector development in the absence of MIG, wt or MIG−/− allografts were performed and purified CD8 T cells were tested by IFN‐γ ELISPOT on d 7 pTx. For MIG−/− donors, the frequency of IFN‐γ‐producing CD8 T cells was 40% lower than wt allografts. With MIG−/− recipients, the frequency of IFN‐γ‐producing T cells approximates naïve levels. To test the role of MIG in graft infiltration, Thy1.1 donor‐primed CD8 T cells were transferred to 1) B6 Thy1.2 allograft recipients or 2) MIG−/− B6 Thy1.2 recipients of MIG−/− allografts. Grafts were harvested on d 2 post‐transfer and analyzed using FACS. Primed CD8 T cells infiltrate allografts equally regardless of MIG in the graft or recipient. Collectively, these data indicate that APCs produce MIG in the priming site and that MIG promotes development of IFN‐γ‐producing effectors. It appears that MIG is not required to recruit primed T cells to the allograft. Work was supported by RO1 A1 51620 and NIH T32 GM07250.