title: Increased numbers and suppressive activity of regulatory CD25(+)CD4(+) T lymphocytes in the absence of CD4 engagement by MHC class II molecules.
abstract: Mechanisms of central and peripheral tolerance prevent autoimmunity. Regulatory T cells inhibit the activation of potentially auto-reactive T cells in peripheral lymphoid organs. In transgenic mice in which all MHC class II molecules are incapable of binding to CD4, class II MHC-restricted T cells preferentially differentiated into immunosuppressive, regulatory T cells. In these mutant MHC class II transgenic mice, a subset of CD4(+) T cells constitutively expressed moderately elevated levels of CD25 and potently inhibited interleukin-2 secretion by T cells from normal mice in a cell-to-cell, contact-dependent manner. Immunosuppressive activity depended on activation of the regulatory T cells. Thus, CD25(+)CD4(+) T cells from mutant MHC class II transgenic mice resembled phenotypically and functionally a major subset of natural regulatory T cells in normal mice, but were two to three-times more abundant. These results further clarify the mechanisms that govern the differentiation and maintenance of CD25(+)CD4(+) regulatory T cells, and present avenues for immunomodulation.
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555-1019, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Shen
authors.forename: Chun
authors.initials: C
authors.lastname: Niu
authors.forename: Rolf
authors.initials: R
authors.lastname: König
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens
keywords: AICD; APC; Ab; Aging mice; CD25; CD4-MHC class II interactions; CD95; Effector/memory T cells; FITC; IFN; IL-2; Immunosuppression; MHC; Naïve T cells; Ova323; R-PE; Regulatory T cells; SEA; SEB; Staphylococcal enterotoxin A; Staphylococcal enterotoxin B; T cell receptor; TCR; Treg; activation-induced cell death; antibody; antigen-presenting cell; fluorescein isothiothyanate; interferon; interleukin-2; major histocompatibility complex; ovalbumin peptide 323-339; phycoerythrin; regulatory T cells