NKT Cells Are Critical for the Initiation of an Inflammatory Bowel Response againstToxoplasma gondii
- 15 July 2005
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 175 (2), 899-908
- https://doi.org/10.4049/jimmunol.175.2.899
Abstract
We demonstrated in this study the critical role of NKT cells in the lethal ileitis induced in C57BL/6 mice after infection with Toxoplasma gondii. This intestinal inflammation is caused by overproduction of IFN-γ in the lamina propria. The implication of NKT cells was confirmed by the observation that NKT cell-deficient mice (Jα281−/−) are more resistant than C57BL/6 mice to the development of lethal ileitis. Jα281−/− mice failed to overexpress IFN-γ in the intestine early after infection. This detrimental effect of NKT cells is blocked by treatment with α-galactosylceramide, which prevents death in C57BL/6, but not in Jα281−/−, mice. This protective effect is characterized by a shift in cytokine production by NKT cells toward a Th2 profile and correlates with an increased number of mesenteric Foxp3 lymphocytes. Using chimeric mice in which only NKT cells are deficient in the IL-10 gene and mice treated with anti-CD25 mAb, we identified regulatory T cells as the source of the IL-10 required for manifestation of the protective effect of α-galactosylceramide treatment. Our results highlight the participation of NKT cells in the parasite clearance by shifting the cytokine profile toward a Th1 pattern and simultaneously to immunopathological manifestation when this Th1 immune response remains uncontrolled.Keywords
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