A stepwise breakdown of B-cell tolerance occurs within renal allografts during chronic rejection

作者:Thaunat Olivier*; Graff Dubois Stephanie; Fabien Nicole; Duthey Aurelie; Attuil Audenis Valerie; Nicoletti Antonino; Patey Natcha; Morelon Emmanuel
来源:Kidney International, 2012, 81(2): 207-219.
DOI:10.1038/ki.2011.317

摘要

Autoantibodies detected after kidney transplantation may contribute to chronic rejection. We and others have previously described the organization of immune effectors into functional intragraft tertiary lymphoid tissue, a site where breakdown of B-cell tolerance may occur. To test this, we performed a comprehensive analysis of 26 chronically rejected kidney grafts. Antibodies were screened by indirect immunofluorescence on HEp2 cells, a procedure that detects antibodies to intracellular antigens, and monkey kidney sections, which detects kidney tissue autoantigens. The incidence of anti-HEp2 autoantibodies was significantly higher in graft explant culture supernatants than in patient sera. Reactivity against monkey kidney sections was detected in almost half of culture supernatants with anti-HEp2 autoantibodies. A local enrichment in T helper 17 and B-cell-activating factor (CD257) correlated with intragraft production of anti-HEp2 antibodies. A decrease in Tregs and a symmetric increase of activated OX40 (CD134)-expressing CD4+ T cells were found in grafts in which anti-kidney autoantibodies were produced. Thus, a stepwise breakdown of B-cell tolerance occurs within the graft during chronic rejection. Hence, the intragraft microenvironment interferes with peripheral deletion of autoreactive immature B cells that, in turn, produce antibodies against intracellular autoantigens. When intragraft immune regulation is insufficient, spreading of the local response against kidney autoantigens is favored. Kidney International (2012) 81, 207-219; doi:10.1038/ki.2011.317; published online 21 September 2011

  • 出版日期2012-1