Reduced susceptibility to dextran sulphate sodium-induced colitis in the interleukin-2 heterozygous (IL-2) mouse.
Summary Mice homozygous for an inactivation of the interleukin-2 (IL-2) gene develop a T-cell dependent colitis. Heterozygous (IL-2+/-) mice are clinically healthy but have been shown to express reduced levels of IL-2 in the colon. Splenocytes from the IL-2+/- mice had a poorer proliferative response to polyclonal T-cell activation and these mice have reduced numbers of intestinal regulatory T cells (CD4+ CD25+ cells) when compared to wild type mice. When exposed to dextran sulphate sodium (DSS) IL-2+/- mice showed a markedly reduced susceptibility to DSS-induced colitis. While DSS treatment caused a marked increase in both CD4+ and CD8+ colonic T cells expressing increased levels of IL-2, IL-4, and IL-10 in wild type mice none of these changes were seen in IL-2+/- mice. On the contrary, cytokine expression in intestinal T cells of IL-2+/- mice was actually reduced after DSS treatment. These results suggest that reduced levels of IL-2 leads to attenuated activation and function of intestinal T cells in IL-2+/- mice and a failure to react adequately to DSS exposure.
Sund
Malin
M
Department of Medicine, University of Umea, Umea, Sweden.
Xu
Li Li
LL
Rahman
Arman
A
Qian
Bi-Feng
BF
Hammarström
Marie-Louise
ML
Danielsson
Ake
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D005260:Female; D005434:Flow Cytometry; D006579:Heterozygote; D007376:Interleukin-2 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015375:Receptors, Interleukin-2 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D016264:Dextran Sulfate