title: CD4(+)CD25(+) T-cell development is regulated by at least 2 distinct mechanisms.
abstract: It has recently been shown that CD4(+)CD25(+) T cells are immunoregulatory T cells that prevent CD4(+) T-cell-mediated organ-specific autoimmune diseases. In this study, the regulatory mechanism of CD4(+)CD25(+) T-cell development were investigated using T-cell receptor (TCR) transgenic mice. It was found that CD4(+)CD25(+) T cells preferentially expressed the endogenous TCRalpha chain in DO10(+) TCR transgenic mice compared with CD4(+)CD25(-) T cells. Moreover, it was found that CD4(+)CD25(+) thymocytes were severely decreased in DO10(+) TCR-alpha(-/-) mice in positively selecting and negatively selecting backgrounds, whereas CD4(+)CD25(-) thymocytes efficiently developed by transgenic TCR in DO10(+) TCR-alpha(-/-) mice in positively selecting backgrounds, indicating that the appropriate affinity of TCR to major histocompatibility complex (MHC) for the development of CD4(+)CD25(+) thymocytes is different from that of CD4(+)CD25(-) thymocytes and that a certain TCR-MHC affinity is required for the development of CD4(+)CD25(+) thymocytes. Finally, it was found that, in contrast to thymus, CD4(+)CD25(+) T cells were readily detected in spleen of DO10(+) TCR-alpha(-/-) mice in positively selecting backgrounds and that splenic CD4(+)CD25(+) T cells, but not CD4(+)CD25(+) thymocytes, were significantly decreased in B-cell-deficient mice, suggesting that B cells may control the peripheral pool of CD4(+)CD25(+) T cells. Together, these results indicate that the development of CD4(+)CD25(+) T cells in thymus and the homeostasis of CD4(+)CD25(+) T cells in periphery are regulated by distinct mechanisms.
authors.affiliation: Department of Internal Medicine II, the Core Research for Evolutional Science and Technology Project, and Chiba University, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
authors.forename: Kei
authors.initials: K
authors.lastname: Ikeda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kubo
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
mesh_terms: D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D017635:Clonal Anergy; D017637:Clonal Deletion / Q000502:physiology*; D003433:Crosses, Genetic; D015329:Gene Rearrangement, T-Lymphocyte; D006183:H-2 Antigens / Q000276:immunology; D006706:Homeostasis; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D009928:Organ Specificity; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D006183:H-2 Antigens; D007148:Immunoglobulin mu-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2