A crucial role of the thymus in induction by the lprcg gene of lymphadenopathy with autoimmunity in the mouse.
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.
Matsuzawa
A
A
Laboratory Animal Research Center, University of Tokyo, Japan.
Moriyama
T
T
Ogata
Y
Y
Katagiri
T
T
Kimura
M
M
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*
D000974:Antibodies, Antinuclear; D000954:Antigens, Surface; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007075:Immunoglobulin M