Intestinal inflammation observed in IL-2R/IL-2 mutant mice is associated with impaired intestinal T lymphopoiesis.
OBJECTIVE
Although interleukin (IL)-2(-/-) and IL-2Ralpha(-/-) mice develop inflammatory bowel disease, IL-2Rbeta(-/-) animals are apparently free of gut pathology. Intraintestinal T lymphopoiesis is reported to be impaired in IL-2Rbeta(-/-) mice; we have determined whether this characteristic correlated with the apparent resistance of this mutant strain to intestinal inflammation. This led us to reassess intraintestinal T lymphopoiesis in these 3 mutant strains.


METHODS
Intestinal histology and intraintestinal T lymphopoiesis were analyzed in unmanipulated mutant mice and in athymic and euthymic radiation chimeras reconstituted with bone marrow derived from IL-2(-/-), IL-2Ralpha(-/-), and IL-2Rbeta(-/-) donors.


RESULTS
Intraintestinal T lymphopoiesis was ablated in the 3 mutant strains and was associated with cryptopatch abnormalities. The intestinal mucosa of mice reconstituted with lymphocytes from IL-2Rbeta(-/-) mice exhibited lesions of both the small and large bowel similar to those observed in the early stages of human gluten enteropathy and acute ulcerative colitis, respectively. Analysis of euthymic and athymic bone marrow radiation chimeras indicated that T cells located in the intestinal mucosa of unmanipulated IL-2(-/-), IL-2Ralpha(-/-), and IL-2Rbeta(-/-) mice are of thymic origin.


CONCLUSIONS
Null mutations at IL-2/IL-2Ralpha and beta loci differentially affect intraintestinal and intrathymic T lymphopoiesis. These conditions are associated with lesions of intestinal inflammation that are mediated by thymus-derived T cells.
Poussier
P
P
Arthritis and Immune Disorder Research Centre, Toronto, University of Toronto, Toronto, Ontario, Canada.
Ning
T
T
Chen
J
J
Banerjee
D
D
Julius
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D004760:Enterocolitis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010641:Phenotype; D011828:Radiation Chimera; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2