title: Murine thymic selection quantified using a unique method to capture deleted T cells.
abstract: Thymic positive and negative selection events generate a T-cell repertoire that is MHC restricted and self-tolerant. The number of T cells undergoing positive and negative selection in normal mice has never been firmly established. We generated mice that lack the proapoptotic molecule Bim (bcl2l11) together with a Nur77(GFP) transgene, which allowed the identification and enumeration of T cells that would normally undergo clonal deletion. Using this method, we report the striking observation that six times more cells undergo negative selection than complete positive selection. Seventy-five percent of the negatively selected cells are deleted at the double positive stage in the thymic cortex, compared with 25% at the single positive stage in the medulla. The fact that more thymocytes are highly reactive to MHC than are weakly reactive is inconsistent with a random model of recognition and suggests that T-cell recognition is MHC biased. Furthermore, Bim(-/-) mice had an increased number of GFP(hi) cells in the peripheral lymphoid tissue and a corresponding increase in antigen experienced or anergic cell phenotype. Our data also show that the CD4+ T cells that are clonally deleted experienced only slightly stronger T-cell receptor signaling than those that developed into regulatory T cells.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55414, USA.
authors.forename: Gretta L
authors.initials: GL
authors.lastname: Stritesky
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.forename: Jami R
authors.initials: JR
authors.lastname: Erickson
authors.forename: Lokesh A
authors.initials: LA
authors.lastname: Kalekar
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Mueller
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology; D000072224:Bcl-2-Like Protein 11; D017637:Clonal Deletion / Q000502:physiology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D006649:Histocompatibility Antigens; D008565:Membrane Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011518:Proto-Oncogene Proteins