Article (Scientific journals)
Autoimmune syndrome after induction of neonatal tolerance to alloantigens: CD4+ T cells from the tolerant host activate autoreactive F1 B cells
Merino, J.; Schurmans, Stéphane; Duchosal, M. et al.
1989In Journal of Immunology, 143, p. 2202-2208
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Keywords :
Autoimmune; alloantigens; CD4+ T cells; induction; neonatal tolerance
Abstract :
[en] The induction of transplantation tolerance to H-2b alloantigens in BALB/c (H-2d) mice by neonatal injection of (C57BL/6 x BALB/c)F1 spleen cells, produces an autoimmune lupus-like syndrome due to an activation of persisting F1 donor B cells. This syndrome is characterized by hypergammaglobulinaemia, high levels of anti-DNA antibodies, as well as by circulating immune complexes and glomerular deposits of Ig. The role of host T cells in this model was investigated by using athymic BALB/c nu/nu mice as recipients of normal (C57BL/6 x BALB.Igb)F1 spleen cells. In these "tolerized" BALB/c nu/nu mice, there was a persistence of F1 donor B cells but none of the autoimmune features were expressed, conversely to tolerized BALB/c nu/+ littermates. The injection of CD4+CD8- T lymphocytes from adult normal BALB/c mice in 3-wk-old tolerized BALB/c nu/nu mice triggered the appearance of all the autoimmune findings observed in euthymic tolerant mice. The autoantibodies were produced by persisting F1 donor B cells as shown by allotype analysis. More strikingly, a similar triggering of the autoimmune syndrome, including high titers of anti-DNA IgG antibodies and circulating immune complexes, was observed after injection of CD4+CD8- T cells from 2-wk-old tolerant BALB/c mice into "tolerized" BALB/c nu/nu mice. The anti-ssDNA antibodies were shown to bear only the Ighb allotype, indicating their exclusive origin from F1 donor B cells. These results imply that CD4+ T cells from the tolerant mice are necessary for the activation of autoreactive F1 B cells and for the development of the autoimmune syndrome occurring in this model. They also suggest that, although there is a marked depletion of H-2b- specific alloreactive CTL precursors in those neonatally tolerized mice, this state of tolerance can be associated with the persistence of H-2b-specific alloreactive CD4+ cells
Disciplines :
Biochemistry, biophysics & molecular biology
Genetics & genetic processes
Author, co-author :
Merino, J.;  Hospital nacional "Marqués de Valdecilla" Santander Spain
Schurmans, Stéphane  ;  Université Libre de Bruxelles - ULB
Duchosal, M.
Izui, S.
Lambert, P. H.;  World Health Organization - WHO Geneva Switzerland
Language :
English
Title :
Autoimmune syndrome after induction of neonatal tolerance to alloantigens: CD4+ T cells from the tolerant host activate autoreactive F1 B cells
Publication date :
1989
Journal title :
Journal of Immunology
ISSN :
0022-1767
eISSN :
1550-6606
Publisher :
American Association of Immunologists, Baltimore, United States - Maryland
Volume :
143
Pages :
2202-2208
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 07 December 2009

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