Type I Interferons Are Not Critical for Skin Allograft Rejection or the Generation of Donor‐Specific CD8+ Memory T Cells

Type I interferons (IFN‐I) link innate to adaptive immunity in microbial infection, autoimmune disease and tumor immunity. It is not known whether IFN‐I have an equally central role in alloimmunity. Here we tested this possibility by studying skin allograft survival and donor‐specific CD8+ T‐cell responses in mice that lack the IFN‐I receptor (IFN‐IR−/−). We found that IFN‐IR−/− mice reject fully allogeneic wild‐type skin grafts at the same rate as wild‐type recipients. Similarly, allograft rejection was not delayed if IFN‐IR−/− male skin was transplanted to syngeneic IFN‐IR−/− female mice. Quantitation of the male (H‐Y)‐specific CD8+ T‐cell response in these mice revealed normal generation of donor‐specific CD8+ effector T cells but fourfold reduction in CD8+ memory T cells. Memory CD8+ T cells generated in the absence of IFN‐IR had normal phenotype and recall function, assessed by ex vivo cytokine production and the ability of IFN‐IR−/− mice to mount second set rejection. Finally, these memory T cells were maintained at a constant number despite their inability to respond to IFN‐1. Our findings indicate that IFN‐I cytokines are not critical for acute allograft rejection or for the expansion and differentiation of donor‐specific CD8+ T cells into long‐lived, functional memory T cells. In a mouse model of skin transplantation, the absence of type I interferon receptor in both the donor and recipient or the recipient alone did not alter allograft rejection or the generation of donor‐specific CD8 memory T cells.