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Autoimmune syndrome after induction of neonatal tolerance to alloantigens. CD4+ T cells from the tolerant host activate autoreactive F1 B cells.
J Immunol 1989; 143(7):2202-8JI

Abstract

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.

Authors+Show Affiliations

WHO Immunology Research and Training Centre, Department of Pathology, Geneva, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2570803

Citation

Merino, J, et al. "Autoimmune Syndrome After Induction of Neonatal Tolerance to Alloantigens. CD4+ T Cells From the Tolerant Host Activate Autoreactive F1 B Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 143, no. 7, 1989, pp. 2202-8.
Merino J, Schurmans S, Duchosal MA, et al. Autoimmune syndrome after induction of neonatal tolerance to alloantigens. CD4+ T cells from the tolerant host activate autoreactive F1 B cells. J Immunol. 1989;143(7):2202-8.
Merino, J., Schurmans, S., Duchosal, M. A., Izui, S., & Lambert, P. H. (1989). Autoimmune syndrome after induction of neonatal tolerance to alloantigens. CD4+ T cells from the tolerant host activate autoreactive F1 B cells. Journal of Immunology (Baltimore, Md. : 1950), 143(7), pp. 2202-8.
Merino J, et al. Autoimmune Syndrome After Induction of Neonatal Tolerance to Alloantigens. CD4+ T Cells From the Tolerant Host Activate Autoreactive F1 B Cells. J Immunol. 1989 Oct 1;143(7):2202-8. PubMed PMID: 2570803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autoimmune syndrome after induction of neonatal tolerance to alloantigens. CD4+ T cells from the tolerant host activate autoreactive F1 B cells. AU - Merino,J, AU - Schurmans,S, AU - Duchosal,M A, AU - Izui,S, AU - Lambert,P H, PY - 1989/10/1/pubmed PY - 1989/10/1/medline PY - 1989/10/1/entrez SP - 2202 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 143 IS - 7 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/2570803/Autoimmune_syndrome_after_induction_of_neonatal_tolerance_to_alloantigens__CD4+_T_cells_from_the_tolerant_host_activate_autoreactive_F1_B_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=2570803 DB - PRIME DP - Unbound Medicine ER -