We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Anti-interleukin-12/23p40 antibody attenuates chronic rejection of cardiac allografts partly via inhibition γδT cells.
- Authors
Wang, S.; Xu, X.; Xie, A.; Li, J.; Ye, P.; Liu, Z.; Wu, J.; Rui, L.; Xia, J.
- Abstract
In our previous study, we showed that treatment with an anti-interleukin (IL)-12/23p40 antibody inhibits acute cardiac allograft rejection via inhibiting production of interferon (IFN)-γ and IL-17a. However, the impact of this antagonistic anti-p40 antibody on chronic cardiac rejection was unclear. Hearts of B6.C-H2bm12/KhEg mice were transplanted into major histocompatibility complex (MHC) class II-mismatched C57Bl/6J mice (wild-type, γδTCR -/- and IL-17-/-), which is an established murine model of chronic allograft rejection without immunosuppression. The mice were treated with control immunoglobulin (Ig)G or 200 µg anti-p40 monoclonal antibody on post-operative days, respectively. Abdominal palpation and echocardiography were used to monitor graft survival. The mice administered with anti-p40 antibody showed a significant promotion in graft survival (median survival time >100 days), and histological analyses revealed that cardiac allograft rejection was attenuated. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence analyses demonstrated that anti-p40 antibody down-regulated the level of ingraft cytokine and chemokine expression (IL-6, IFN-γ, IL-17a, CCL2 and CCL20). Flow cytometry analyses showed that γδ T cells are an important ingraft source of IFN-γ and IL-17a and inhibit the production of inflammation cytokine by anti-p40 antibody. Compared with the wild-type group, the graft survival time in the γδ T cell receptor-/- and IL-17-/- mice was prolonged significantly. Therefore we propose that, in the chronic allograft rejection model, treatment with anti-p40 antibody prolongs graft survival possibly by reducing the amount of reactive inflammatory cells, especially γδ T cells.
- Subjects
INTERLEUKINS; IMMUNOGLOBULINS; HOMOGRAFTS; T cells; GRAFT rejection; HISTOCOMPATIBILITY; POLYMERASE chain reaction
- Publication
Clinical & Experimental Immunology, 2012, Vol 169, Issue 3, p320
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/j.1365-2249.2012.04612.x