Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 3, Pages 1886-1894Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.3.1886
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Funding
- NCI NIH HHS [R01 CA137869-01A2, R01 CA137869] Funding Source: Medline
- NIAID NIH HHS [R21 AI052266, R01 AI052266, R56 AI052266, AI052266] Funding Source: Medline
- NIDDK NIH HHS [DK069594, R21 DK069594, R01 DK099076] Funding Source: Medline
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Abnormal T cell responses to commensal bacteria are involved in the pathogenesis of inflammatory bowel disease. MyD88 is an essential signal transducer for TLRs in response to the microflora. We hypothesized that TLR signaling via MyD88 was important for effector T cell responses in the intestine. TLR expression on murine T cells was examined by flow cytometry. CD4(+)CD45Rb(high) T cells and/or CD4(+)CD45Rb(low)CD25(+) regulatory T cells were isolated and adoptively transferred to RAG1(-/-) mice. Colitis was assessed by changes in body weight and histology score. Cytokine production was assessed by ELISA. In vitro proliferation of T cells was assessed by [H-3]thymidine assay. In vivo proliferation of T cells was assessed by BrdU and USE labeling. CD4(+)CD45Rb(high) T cells expressed TLR2, TLR4, TLR9,and TLR3, and TLR ligands could act as costimulatory molecules. MyD88(-/-) CD4(+) T cells showed decreased proliferation compared with WT CD4(+) T cells both in vivo and in vitro. CD4(+)CD45Rb(high) T cells from MyD88(-/-) mice did not induce wasting disease when transferred into RAG1(-/-) recipients. Lamina propria CD4(+) T cell expression of IL-2 and IL-17 and colonic expression of IL-6 and IL-23 were significantly lower in mice receiving MyD88(-/-) cells than mice receiving WT cells. In vitro, MyD88(-/-) T cells were blunted in their ability to secrete IL-17 but not IFN-gamma. Absence of MyD88 in CD4(+)CD45Rb(high) cells results in defective T cell function, especially Th17 differentiation. These results suggest a role for TLR signaling by T cells in the development of inflammatory bowel disease.
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