title: A crucial role of the thymus in induction by the lprcg gene of lymphadenopathy with autoimmunity in the mouse.
abstract: The new mutation at the lpr locus, lprcg, induces massive lymphoproliferation characterized by the selective expansion of CD4-, CD8-, B220+, Thy-1+ cells or double-negative T lymphocytes and production of autoantibodies as does lpr. The thymus is necessary for the induction of anomalous double-negative T lymphocytes and autoimmune symptoms by lpr. To determine whether or not the thymus is also indispensable to expression of the function of lrpcg, lprcg homozygous athymic nude mice (lprcg/lprcg nu/nu; lprcg nudes) were constructed by crossing CBA/KlJms-lprcg/lprcg (CBA-lprcg) and DDD/l-nu/nu mice and observed for lymphoid organ hyperplasia and autoantibody production with or without thymus grafts from various strains of mice including CBA-lprcg. Neither lymphoproliferation nor significantly increased production of autoantibodies was observed in unmanipulated lprcg nudes. In contrast, thymus grafts of both +/+ and lprcg/lprcg genotypes caused lymphoid organ hyperplasia composed of anomalous double-negative T lymphocytes and significantly augmented the production of antibodies against single-stranded DNA (ssDNA). Interestingly, serum Ig and anti-ssDNA antibody levels rose in response to thymus grafts only in IgG but not in IgM classes. These results indicate that the thymus plays a crucial role in the induction of abnormal T-cell differentiation by lprcg and that thymic genotype is irrelevant.
authors.affiliation: Laboratory Animal Research Center, University of Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsuzawa
authors.forename: T
authors.initials: T
authors.lastname: Moriyama
authors.forename: Y
authors.initials: Y
authors.lastname: Ogata
authors.forename: T
authors.initials: T
authors.lastname: Katagiri
authors.forename: M
authors.initials: M
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology; D005808:Genes, Recessive / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology; D008206:Lymphatic Diseases / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D000954:Antigens, Surface; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007075:Immunoglobulin M