CD4+ CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses.
Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4+CD25+ regulatory T cells (CD25+ Treg). To explore the functional development of autoantigen-reactive CD25+ Treg in humans we investigated if thymic CD25+ Treg from children aged 2 months to 11 years and cord blood CD25+ Treg are able to suppress proliferation and cytokine production induced by specific antigens. While CD4+CD25- thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25+ Treg. However, CD25+ Treg inhibited interferon (IFN)-gamma production induced by MOG, which indicates that MOG-reactive CD25+ Treg are present in the thymus. In contrast, cord blood CD25+ Treg suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25+ Treg expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25+ T cells. Further characterization of cord blood CD25+ T cells revealed that FOXP3 was highly expressed by CD25+CD45RA+ cells while CD25+CD45RA- cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25+ T cells compared to thymic CD25+ T cells. In conclusion, our data demonstrate that low numbers of MOG-reactive functional CD25+ Treg are present in normal thymus, but that the suppressive ability of the cells is broader in cord blood. This suggests that the CD25+ Treg may be further matured in the periphery after being exported from the thymus.
Wing
Kajsa
K
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Larsson
Pia
P
Sandström
Kerstin
K
Lundin
Samuel B
SB
Suri-Payer
Elisabeth
E
Rudin
Anna
A
D000954:Antigens, Surface / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005312:Fetal Blood / Q000276:immunology*; D051858:Forkhead Transcription Factors; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000954:Antigens, Surface; D004268:DNA-Binding Proteins; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007378:Interleukins; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma