期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 8, 期 8, 页码 1622-1630出版社
WILEY
DOI: 10.1111/j.1600-6143.2008.02295.x
关键词
antibodies; complement; transplantation
资金
- NHLBI NIH HHS [R01 HL56086, R01 HL056086, R01 HL070613-06, R01 HL070613, R01 HL052886, R01 HL056086-13, R01 HL52886, R01 HL052886-13] Funding Source: Medline
- NIAID NIH HHS [R01 AI061469-04, R01 AI061469] Funding Source: Medline
Though complement (C) deposition within the transplant is associated with allograft rejection, the pathways employed have not been established. In addition, evidence suggests that C-mediated cytolysis may be necessary for the tolerance-inducing activities of mAb therapies. Hence, we assessed the role of the classical C pathway in acute allograft rejection and its requirement for experimental mAb therapies. C1q-deficient (C1q-/-) recipients rejected allografts at a faster rate than wild-type (WT) recipients. This rejection was associated with exacerbated graft pathology but not with enhanced T-cell responses in C1q-/- recipients. However, the humoral response to donor alloantigens was accelerated in C1q-/- mice, as an early IgG response and IgG deposition within the graft were observed. Furthermore, deposition of C3d, but not C4d was observed in grafts isolated from C1q-/- recipients. To assess the role of the classical C pathway in inductive mAb therapies, C1q-/- recipients were treated with anti-CD4 or anti-CD40L mAb. The protective effects of anti-CD4 mAb were reduced in C1q-/- recipients, however, this effect did not correlate with ineffective depletion of CD4+ cells. In contrast, the protective effects of anti-CD40L mAb were less compromised in C1q-/- recipients. Hence, this study reveals unanticipated roles for C1q in the rejection process.
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