CD4+CD25+ regulatory T cells specific for a thymus-expressed antigen prevent the development of anaphylaxis to self.

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.

• Authors: Stefano Scabeni, Marilena Lapilla, Silvia Musio, Barbara Gallo, Emilio Ciusani, Lawrence Steinman, Renato Mantegazza, Rosetta Pedotti
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 7 Pg. 4433-40 (Apr 01 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18354164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Antigens
• Immunoglobulin G
• Myelin Proteolipid Protein
• Interleukin-10
• Interferon-gamma

Topics

• Anaphylaxis (immunology, metabolism, pathology, prevention & control)
• Animals
• Antibodies (immunology)
• Antigens (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Proliferation
• Cells, Cultured
• Female
• Immunization
• Immunoglobulin G (immunology)
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis)
• Lymph Nodes (immunology, metabolism)
• Mice
• Myelin Proteolipid Protein (immunology)
• Self Tolerance (immunology)
• Thymus Gland (immunology)