Autoimmune syndrome after induction of neonatal tolerance to alloantigens: analysis of the role of donor T cells in the induction of autoimmunity.
The injection of (C57BL/6 x BALB/c) F1 spleen cells into BALB/c newborn mice leads to activation of persisting F1 donor B cells and development of a lupus-like syndrome in tolerized BALB/c mice. This syndrome is characterized by hypergammaglobulinaemia, high levels of anti-DNA and anti-Sm antibodies, circulating immune complexes and deposits of immunoglobulin in renal glomeruli. The role of donor T cells in this model was investigated by injecting the newborn mice with F1 cells depleted in different T cell subsets by using specific monoclonal antibodies (MoAbs). Tolerance, as shown by an absence of H-2b-specific CTL alloreactivity and persistence of immunoglobulin bearing the donor allotype were observed in mice injected with F1 cells previously depleted in the CD4+ and/or CD8+ T cell subsets as well as in those which received Thy-1+-depleted F1 spleen cells. In these mice, a typical autoimmune syndrome was found, including splenomegaly and lymphadenopathy, anti-ssDNA and anti-aortic myosin IgG antibodies and renal deposition of immunoglobulin. However, some quantitative changes were seen: the levels of anti-aortic myosin antibodies were lower in mice tolerized with CD4+-depleted F1 cells than in those receiving untreated F1 cells. Conversely, higher levels of these autoantibodies were observed in mice tolerized with CD8+-depleted F1 cells. These results suggest that mature donor T cells are not necessary neither for the establishment of neonatal tolerance to alloantigens nor for the activation of F1 donor B cells in the production of the autoimmune syndrome in tolerant mice, but they may contribute in the regulation of the expression of autoreactive B cell clones.
Merino
J
J
Department of Pathology, Centre Medical Universitaire, Geneva, Switzerland.
Schurmans
S
S
Wen
L
L
Brighouse
G
G
Luzuy
S
S
Lambert
P H
PH
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007116:Immunization, Passive; D007519:Isoantigens / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D007519:Isoantigens; D018800:Thy-1 Antigens