| First Author | Wang S | Year | 2012 |
| Journal | Clin Exp Immunol | Volume | 169 |
| Issue | 3 | Pages | 320-9 |
| PubMed ID | 22861372 | Mgi Jnum | J:188287 |
| Mgi Id | MGI:5440129 | Doi | 10.1111/j.1365-2249.2012.04612.x |
| Citation | Wang S, et al. (2012) Anti-interleukin-12/23p40 antibody attenuates chronic rejection of cardiac allografts partly via inhibition gammadeltaT cells. Clin Exp Immunol 169(3):320-9 |
| abstractText | 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)-gamma 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, gammadeltaTCR (-/-) 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 microg 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-gamma, IL-17a, CCL2 and CCL20). Flow cytometry analyses showed that gammadelta T cells are an important ingraft source of IFN-gamma 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 gammadelta 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 gammadelta T cells. |
