Nonlittermate Rip2^−/−Rag1^−/− mice develop accelerated colitis. Nonlittermate Rip2^−/−Rag1^−/− and Rag1^−/− mice were injected i.p. with 0.5 × 10⁶ CD45RB^High CD4 T cells. (A) Mice were weighed weekly, and the percentage of initial body weight was calculated. Data from four experiments were pooled, n = 15 mice per group. (B) Mice were sacrificed at week 4. Colons were fixed, H&E stained, and scored for colitis severity. Data from three experiments were pooled. (C) Representative spleens and colons were imaged. (D and E) Spleen, colon LP, and MLNs were harvested at week 4, and isolated cells were quantified by flow cytometry. (F and G) Colon cells were restimulated with plate-bound anti-CD3/anti-CD28 antibody and analyzed by flow cytometry to determine the total (F) and frequency (G) of cytokine-positive cells. Data from three experiments were pooled with 5–15 mice per group. (H) Proximal colon explants were cultured for 18 h, and supernatants were analyzed by ELISA for cytokine production. Data from two experiments were pooled with four to seven samples per group. (A, B, and D–H) Mean ± SEM is shown with *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001 using an unpaired Student’s t test.