[en] The injection of semi-allogeneic F1 spleen cells into newborn mice of a parental strain induces a state of immune tolerance characterized by anti-donor CTL unresponsiveness and the appearance of a transient SLE-like autoimmune syndrome associating autoantibody production, hypergammaglobulinemia, splenomegaly and glomerulonephritis. Our previous experiments have demonstrated that host Th2-like CD4+ T lymphocytes activate donor F1 B cells persisting in the host to produce autoantibodies, and that this cellular interaction relies on the presence of alloMHC class II molecules on donor B cells. In order to investigate the role and the involvement of MHC alloantigens in the cellular T(host)-B(donor) interaction, newborn C57BL/6 (B6) mice were injected with F1 spleen cells differing from the host at the level of defined portions of the MHC class I (K) or class II (I-A and I-E) molecules. B6 mice injected at birth with spleen cells from different F1 strains were tolerant to each alloantigen (alloAg) tested, as assessed by specific anti-donor CTL unresponsiveness. However, the SLE-like autoimmune syndrome only developed in B6 mice injected at birth with F1 spleen cells differing at the level of MHC class II I-A or I-E molecules. Autoantibodies appeared later in B6 mice neonatally tolerized to I-E alloAg than those detected in B6 mice neonatally tolerized to I-A alloAg. These results show that the SLE-like autoimmune disease that develops concomitantly to neonatally-induced tolerance to alloAg is the consequence of cognate T host-B donor cellular interactions triggered by even minute differences in the MHC class II I-A or MHC class II I-E molecules
Kramar, G.; World Health Organization-Immunology Research and Training Center, Department of Pathology, CMU, 1211 Geneva 4,
Schurmans, Stéphane ; Université Libre de Bruxelles - ULB > Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Institut de Biologie et de Médecine Moléculaire
Berney, M.; World Health Organization-Immunology Research and Training Center, Department of Pathology, CMU, 1211 Geneva 4,
Izui, S.; World Health Organization-Immunology Research and Training Center, Department of Pathology, CMU, 1211 Geneva 4,
del Giudice, G.; Institute of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
Lambert, P. H.
Language :
English
Title :
Autoimmunity following neonatal tolerance to alloantigens: role of donor I-A and I-E molecules
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