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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 DO11.10xIL-10(-/-) cells, indicating that secretion of this cytokine by antigen-specific cells is not required.

Original publication

DOI

10.1002/1521-4141(2002010)32:10<2997::AID-IMMU2997>3.0.CO;2-D

Type

Journal article

Journal

Eur J Immunol

Publication Date

10/2002

Volume

32

Pages

2997 - 3006

Keywords

Abatacept, Animals, Antigens, CD, Antigens, Differentiation, CD4-Positive T-Lymphocytes, CTLA-4 Antigen, Immune Tolerance, Immunoconjugates, Interleukin-10, Intestinal Mucosa, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Ovalbumin, Receptors, Antigen, T-Cell