CD4 and colitis: While protection from colitis in Trem1−/− x Rag2−/− mice was associated with reduced expression of several pro-inflammatory mediators, previous data generated in our laboratory have demonstrated that TNF produced by nonlymphoid cells plays a non-redundant pathogenic role in the CD4+ T cell transfer model of colitis since Tnf−/− x Rag2−/− mice are completely protected from colitis induction [38].