CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance.

Journal article

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.

Authors: Fowler, S; Powrie, F

• Publication status: Published
• Journal: European journal of immunology
• Volume: 32
• Issue: 10
• Pages: 2997-3006
• Publication date: 2002-10-01
• DOI: 10.1002/1521-4141(2002010)32:10<2997::aid-immu2997>3.0.co;2-d
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Immune Tolerance; Immunoconjugates; Animals; CD4-Positive T-Lymphocytes; Antigens, CD; CTLA-4 Antigen; Mice; Receptors, Antigen, T-Cell; Lymphocyte Activation; Intestinal Mucosa; Interleukin-10; Ovalbumin; Antigens, Differentiation; Mice, Inbred BALB C