title: In CD8+ T cell-deficient lpr/lpr mice, CD4+B220+ and CD4+B220- T cells replace B220+ double-negative T cells as the predominant populations in enlarged lymph nodes.
abstract: Mice homozygous for lpr or gld develop autoimmunity and progressive lymphoproliferative disease characterized by the accumulation of two unusual populations of B220+ TCR-alpha beta+ T cells, a predominant CD4-CD8- double-negative (DN) subset and a minor CD4dull+ subset. B220+ DN T cells appear to be derived from negatively selected thymocytes, but their immediate precursors have not been identified conclusively, and their relationship to CD4+B220+ T cells is unclear. Our previous studies of lpr and gld mice treated chronically with anti-CD8 mAb provided evidence that the majority of B220+ DN T cells are unrelated to CD4+B220+ T cells and may be descended from peripheral thymus-derived CD8+ T cells. To investigate the contributions of MHC class I-selected thymus-derived T cells to the production of B220+ DN T cells and to the accumulation of CD4+ T cell subsets, we studied C3H-lpr and -gld mice rendered deficient in CD8+ T cells by the introduction of disrupted beta 2-microglobulin (beta 2-m) genes. These CD8+ T cell-deficient mice developed massively enlarged lymph nodes, in which CD4+B220+ T cells and CD4+ T cells replaced B220+ DN T cells as the dominant T cell subsets. As a population, the CD4+B220+ T cells were depleted of autoreactive populations specific for endogenous retroviral superantigens and were enriched for V beta 8.3+ T cells. The deficiency of CD8+ T cells in beta 2-m(-/-)-lpr mice had no effects on the accumulation of primed CD4+ T cells or autoreactive B cells. The selective reduction in B220+ DN T cells and corresponding accumulation of CD4+B220+ T cells in beta 2-m(-/-)-lpr mice provide strong evidence that 1) the majority of B220+ DN T cells are unrelated to CD4+ T cells and their development and/or accumulation is dependent on MHC class I expression; and 2) CD4+B220+ T cells are a remarkably similar, but separate, lineage of cells that develop independently of thymus-derived CD8+ T cells and class I MHC expression.
authors.affiliation: Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: T
authors.initials: T
authors.lastname: Giese
authors.forename: W F
authors.initials: WF
authors.lastname: Davidson
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D001323:Autoantibodies / Q000097:blood; D015139:Blotting, Southern; D015704:CD4 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D000954:Antigens, Surface; D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D001613:beta 2-Microglobulin; D017493:Leukocyte Common Antigens