CD4+CD25+ T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells.
Thymic-derived, naturally occurring, CD4+CD25+ regulatory T cells (nTreg) are potent suppressors of immune responses. A detailed understanding of which components of the development and activation of pathogenic effector T cells are inhibited by nTreg during the course of T cell-mediated, organ-specific autoimmunity is as yet unknown. We have analyzed the effects of polyclonal nTreg on the development of autoimmune gastritis. The nTreg inhibited the development of disease, but failed to inhibit the migration of effector cells into the gastric lymph node or stomach. Notably, nTreg did not inhibit the expansion of autoreactive T cells in the gastric lymph node. The primary effect of nTreg appeared to be inhibition of differentiation of autoantigen-specific T cells to Th1 effector cells, as reflected by a decrease in Ag-stimulated IFN-gamma production and a reduction in T-bet expression.
DiPaolo
Richard J
RJ
Section of Cellular Immunology, Laboratory of Immunology, National Institutes of Health, Bethesda, MD 20892-1892, USA.
Glass
Deborah D
DD
Bijwaard
Karen E
KE
Shevach
Ethan M
EM
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control*; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D005260:Female; D005756:Gastritis / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*
D015704:CD4 Antigens; D015375:Receptors, Interleukin-2