Interleukin-10- mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen.
Regulatory T cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-gamma or to secrete the regulatory cytokine interleukin 10 when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4(+) phenotype. Serial results from individual patients demonstrated that this bias toward proliferative or interleukin-10 responses was unstable over time and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin 10 and dependent on cytotonic T lymphocyte- associated antigen (CTLA-4) costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease.[1]References
- Interleukin-10-mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen. Hall, A.M., Ward, F.J., Vickers, M.A., Stott, L.M., Urbaniak, S.J., Barker, R.N. Blood (2002) [Pubmed]
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