1. CD4+CD25+ regulatory T cells specific for a thymus-expressed antigen prevent the development of anaphylaxis to self.
- Author
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Scabeni S, Lapilla M, Musio S, Gallo B, Ciusani E, Steinman L, Mantegazza R, and Pedotti R
- Subjects
- Anaphylaxis metabolism, Anaphylaxis pathology, Animals, Antibodies immunology, Cell Proliferation, Cells, Cultured, Female, Immunization, Immunoglobulin G immunology, Interferon-gamma biosynthesis, Interleukin-10 biosynthesis, Lymph Nodes immunology, Lymph Nodes metabolism, Mice, Myelin Proteolipid Protein immunology, Anaphylaxis immunology, Anaphylaxis prevention & control, Antigens immunology, CD4-Positive T-Lymphocytes immunology, Self Tolerance immunology, Thymus Gland immunology
- Abstract
A role for CD4(+)CD25(+) regulatory T cells (Tregs) in the control of allergic diseases has been postulated. We developed a mouse model in which anaphylaxis is induced in SJL mice by immunization and challenge with the fragment of self myelin proteolipid protein (PLP)(139-151), that is not expressed in the thymus, but not with fragment 178-191 of the same protein, that is expressed in the thymus. In this study, we show that resistance to anaphylaxis is associated with naturally occurring CD4(+)CD25(+) Tregs specific for the self peptide expressed in the thymus. These cells increase Foxp3 expression upon Ag stimulation and suppress peptide-induced proliferation of CD4(+)CD25(-) effector T cells. Depletion of Tregs with anti-CD25 in vivo significantly diminished resistance to anaphylaxis to PLP(178-191), suggesting an important role for CD4(+)CD25(+) Tregs in preventing the development of allergic responses to this thymus-expressed peptide. These data indicate that naturally occurring CD4(+)CD25(+) Tregs specific for a peptide expressed under physiological conditions in the thymus are able to suppress the development of a systemic allergic reaction to self.
- Published
- 2008
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