CD4+CD25+ regulatory T cells specific for a thymus-expressed antigen prevent the development of anaphylaxis to self.
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.
Scabeni
Stefano
S
Immunology and Muscular Pathology Unit, Neurological Institute Foundation Carlo Besta, Milan, Italy.
Lapilla
Marilena
M
Musio
Silvia
S
Gallo
Barbara
B
Ciusani
Emilio
E
Steinman
Lawrence
L
Mantegazza
Renato
R
Pedotti
Rosetta
R
D000707:Anaphylaxis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D007074:Immunoglobulin G; D018991:Myelin Proteolipid Protein; D016753:Interleukin-10; D007371:Interferon-gamma