CD4 T cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T cells.
Regulatory T cells expressing CD25 have been shown to protect rodents from organ-specific autoimmune diseases. Similar CD25+ cells with a memory phenotype exerting suppressive function after polyclonal or allogeneic stimulation are also present in adult human blood. We demonstrate that adult human CD25+ cells regulate the response to myelin oligodendrocyte glycoprotein (MOG), as depletion of CD25(+) cells increases responses of PBMC and the addition of purified CD25+ cells suppresses MOG-specific proliferation and IFN-gamma production of CD4(+)CD25(-) T cells. In contrast, cord blood CD25+ cells do not inhibit responses to self antigens, and only a small subpopulation of cord CD25+ cells expresses the typical phenotype of adult regulatory T cells (CD45RA(-) and GITR(+)) enabling suppression of polyclonal responses. We conclude that activation of self-reactive T cells in normal healthy individuals is prevented by the presence of self-antigen-specific CD25+ regulatory T cells and that the majority of these cells mature after birth.
Wing
Kajsa
K
Department of Rheumatology and Inflammation Research, University of Göteborg, Guldhedsgatan 10A, S-41346 Göteborg, Sweden. kajsa.wing@rheuma.gu.se
Lindgren
Susanne
S
Kollberg
Gittan
G
Lundgren
Anna
A
Harris
Robert A
RA
Rudin
Anna
A
Lundin
Samuel
S
Suri-Payer
Elisabeth
E
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005312:Fetal Blood / Q000276:immunology*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D053450:Glucocorticoid-Induced TNFR-Related Protein; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human