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CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance by Sanna Fowler; Fiona Powrie is a Immunology and Microbiology article available to read on EtoBox.

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CD4(+) T cells play a vital role in mediating the tolerance induced at mucosal sites following exposure to non-pathogenic stimuli, and further understanding of the precise mechanisms by which these cells prevent aberrant responses is required. We have developed a model using transfer of DO11.10 TCR-transgenic bone marrow into irradiated recipients in which it has been possible to track antigen-specific CD4(+) cells in mesenteric lymph nodes (mLN), Peyer's patches (PP) and lamina propria following primary exposure to antigen. Using this model we have demonstrated initial activation in all three gut-associated lymphoid tissue compartments characterized by increases in the frequency of transgenic cells expressing CD69 and CD25. These cells subsequently enter a state of hyporesponsiveness both locally in the mLN and PP and in the periphery following feeding and challenge. Investigating the role of CTLA-4 either using anti-CTLA-4 mAb or by generating chimeras using DO11.10xCTLA-4(-/-) mice as donors we have clearly shown that antigen-specific cells require the expression of this regulatory molecule for oral tolerance. In contrast, oral tolerance was intact in chimeras generated using DO

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Author

Sanna Fowler; Fiona Powrie

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Ltd.; Wiley (ISSN 0014-2980)

Published

2002

Language

EN

Field

Immunology and Microbiology (Life Sciences)