Intestinal inflammation observed in IL-2R/IL-2 mutant mice is associated with impaired intestinal T lymphopoiesis

Background & Aims: Although interleukin (IL)-2(-/-) and IL-2R alpha(-/-) mi ce develop inflammatory bowel disease, IL-2R beta(-/-) animals are apparent ly free of gut pathology, Intraintestinal T lymphopoiesis is reported to be impaired in IL-2R beta(-/-) mice; we have determined whether this characte ristic correlated with the apparent resistance of this mutant strain to int estinal inflammation, This led us to reassess intraintestinal T lymphopoies is in these 3 mutant strains. Methods: Intestinal histology and intraintest inal T lymphopoiesis were analyzed in unmanipulated mutant mice and in athy mic and euthymic radiation chimeras reconstituted with bone marrow derived from IL-2(-/-), IL-2R alpha(-/-), and IL-2R beta(-/-) donors. Results: Intr aintestinal T lymphopoiesis was ablated in the 3 mutant strains and was ass ociated with cryptopatch abnormalities. The intestinal mucosa of mice recon stituted with lymphocytes from IL-2R beta(-/-) mice exhibited lesions of bo th the small and large bowel similar to those observed in the early stages of human gluten enteropathy and acute ulcerative colitis, respectively. Ana lysis of euthymic and athymic bone marrow radiation chimeras indicated that T cells located in the intestinal mucosa of unmanipulated IL-2(-/-), IL-2R alpha(-/-), and IL-2R beta(-/-) mice are of thymic origin. Conclusions: Nu ll mutations at IL-2/IL-2R alpha and beta loci differentially affect intrai ntestinal and intrathymic T lymphopoiesis. These conditions are associated with lesions of intestinal inflammation that are mediated by thymus-derived T cells.