Maximal inflammatory response benefits syngeneic skin graft acceptance

Objective and design: We investigated the influence of acute inflammation in skin isograft acceptance. Methods: Two mouse lines selected for maximal (AIR_MAX) or minimal inflammatory response (AIR_MIN) were transplanted with syngeneic skin. Cellular infiltrates and cytokine production were measured 1, 3, 7 or 14 days post-transplantation. The percentage of CD4⁺CD25⁺Foxp3⁺ cells in the lymph nodes was also evaluated. Results: Grafts were totally accepted in 100% of AIR_MAX and in 26% of AIR_MIN mice. In the latter, partial acceptance was observed in 74% of the animals. Emigrated cells were basically PMN and were enhanced in AIR_MAX transplants. IL-10 production by graft infiltrating cells showed no interline differences. IFN-γ was increased in AIR_MIN grafts at day 14 and lower percentages of CD4⁺CD25⁺Foxp3⁺ cells in the lymph nodes were observed in these mice. Conclusions: Our data suggest that differences in graft acceptance might be due to a lack of appropriate regulation of the inflammatory response in AIR_MIN mice compromising the self/non-self recognition. Received 30 July 2007; returned for revision 10 October 2007; received from final revision 18 October 2007; accepted by G. Wallace 30 November 2007