title: Reduced development of CD4-8-B220+ T cells but normal autoantibody production in lpr/lpr mice lacking major histocompatibility complex class I molecules.
abstract: The lpr gene has recently been shown to encode a functional mutation in the Fas receptor, a molecule involved in transducing apoptotic signals. Mice homozygous for the lpr gene develop an autoimmune syndrome accompanied by massive accumulation of double-negative (DN) CD4-8-B220+ T cell receptor-alpha/beta+ cells. In order to investigate the origin of these DN T cells, we derived lpr/lpr mice lacking major histocompatibility complex (MHC) class I molecules by intercrossing them with beta 2-microglobulin (beta 2m)-deficient mice. Interestingly, these lpr beta 2m-/- mice develop 13-fold fewer DNT cells in lymph nodes as compared to lpr/lpr wild-type (lprWT) mice. Analysis of anti-DNA antibodies and rheumatoid factor in serum demonstrates that lpr beta 2m-/- mice produce comparable levels of autoantibodies to lprWT mice. Collectively our data indicate that MHC class I molecules control the development of DN T cells but not autoantibody production in lpr/lpr mice and support the hypothesis that the majority of DN T cells may be derived from cells of the CD8 lineage.
authors.affiliation: Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Ohteki
authors.forename: M
authors.initials: M
authors.lastname: Iwamoto
authors.forename: S
authors.initials: S
authors.lastname: Izui
authors.forename: H R
authors.initials: HR
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin; D017493:Leukocyte Common Antigens