IFNγ differentially controls IPS and GVHD of the GI tract by direct signaling through nonhematopoietic host tissue. (A) Mixed chimeric mice were generated by transplanting wt or IFNγR^−/− bone marrow into irradiated (1000 rad) wt or IFNγR^−/− recipients as described in “Materials and methods.” After 3 months, these chimeric mice were phenotyped using CD45.1/CD45.2 disparity to ensure APCs (F4/80⁺ macrophages, CD19⁺ B cells, and CD11c⁺ DCs) had fully reconstituted as donor within lung tissue. The mixed chimeric B6 mice were then used as recipients (conditioned with 950 rad total body irradiation and given transplants of G-CSF–mobilized Balb/c donor splenocytes). In some cases, TCD splenocytes were transplanted as non-GVHD controls. (B) Representative lung (top) or GI tract (bottom) in the recipient chimeras (100 ×). (C) Semiquantitative histologic analysis of transplant chimera recipients as described in “Materials and methods.” Data represent mean plus or minus SE of individual animals combined from 2 replicate experiments. n = 6-15 in T-cell–replete groups and n = 4-7 in TCD groups. ***P < .001, wt → wt and IFNγR^−/− → wt versus wt → IFNγR^−/− and IFNγR^−/− → IFNγR^−/− as shown. ND indicates no pathology detected.