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CD4⁺CD25⁺ Regulatory T Cells Specific for a Thymus-Expressed Antigen Prevent the Development of Anaphylaxis to Self¹

Stefano Scabeni^*, Marilena Lapilla^*, Silvia Musio^*, Barbara Gallo^*, Emilio Ciusani, Lawrence Steinman^,, Renato Mantegazza^* and Rosetta Pedotti^2,*

^* Immunology and Muscular Pathology Unit and Laboratory of Analysis, Neurological Institute Foundation "Carlo Besta," Milan, Italy; and Department of Neurology and Neurological Sciences and Interdepartmental Program in Immunology, Stanford University, Stanford, CA 94305

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This investigation was supported by grants from the National Multiple Sclerosis Society, New York, Fondazione Italiana Sclerosi Multipla (2003/R/42), Ministero della Sanita ("ricerca finalizzata"), and Cariplo Foundation (to R.P.).

² Address correspondence and reprint requests to Dr. Rosetta Pedotti, Immunology and Muscular Pathology Unit, Neurological Institute Foundation "Carlo Besta," Via Celoria 11, 21033 Milan, Italy. E-mail address: rpedotti{at}istituto-besta.it

³ Abbreviations used in this paper: PLP, myelin proteolipid protein; EAE, experimental autoimmune encephalomyelitis; MBP, myelin basic protein; Treg, regulatory T cell; LNC, lymph node cell.

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The JI 2008 180: 4349-4350. [Full Text]