title: Selenoproteins mediate T cell immunity through an antioxidant mechanism.
abstract: Selenium is an essential dietary element with antioxidant roles in immune regulation, but there is little understanding of how this element acts at the molecular level in host defense and inflammatory disease. Selenium is incorporated into the amino acid selenocysteine (Sec), which in turn is inserted into selenoproteins in a manner dependent on Sec tRNA([Ser]Sec). To investigate the molecular mechanism that links selenium to T cell immunity, we generated mice with selenoprotein-less T cells by cell type-specific ablation of the Sec tRNA([Ser]Sec) gene (trsp). Herein, we show that these mutant mice exhibit decreased pools of mature T cells and a defect in T cell-dependent antibody responses. We also demonstrate that selenoprotein deficiency leads to oxidant hyperproduction in T cells and thereby suppresses T cell proliferation in response to T cell receptor stimulation. These findings offer novel insights into immune function of selenium and physiological antioxidants.
authors.affiliation: Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Shrimali
authors.forename: Robert D
authors.initials: RD
authors.lastname: Irons
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Carlson
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Sano
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D051140:Selenoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D012346:RNA, Transfer, Amino Acyl; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D051140:Selenoproteins; C112705:selenocysteinyl-tRNA