Changes in the Transcriptome in Allograft Rejection: IFN‐γ‐Induced Transcripts in Mouse Kidney Allografts

We used Affymetrix Microarrays to define interferon‐γ (IFN‐γ)‐dependent, rejection‐induced transcripts (GRITs) in mouse kidney allografts. The algorithm included inducibility by recombinant IFN‐γ in kidneys of three normal mouse strains, increase in kidney allografts in three strain combinations and less induction in IFN‐γ‐deficient allografts. We identified 40 transcripts, which were highly IFN‐γ inducible (e.g. Cxcl9, ubiquitin D, MHC), and 168 less sensitive to IFN‐γ in normal kidney. In allografts, expression of GRITs was intense and consistent at all time points (day 3 through 42). These transcripts were partially dependent on donor IFN‐γ receptors (IFN‐γrs): receptor‐deficient allografts manifested up to 76% less expression, but some transcripts were highly dependent (ubiquitin D) and others relatively independent (Cxcl9). Kidneys of hosts rejecting allografts showed expression similar to that observed with IFN‐γ injections. Many GRITs showed transient IFN‐γ‐dependent increase in isografts, peaking at day 4–5. GRITs were increased in heart allografts, indicating them as generalized feature of alloresponse. Thus, expression of rejection‐induced transcripts is robust and consistent in allografts, reflecting the IFN‐γ produced by the alloresponse locally and systemically, acting via host and donor IFN‐γr, as well as local IFN‐γ production induced by post‐operative stress.