| First Author | Harbers SO | Year | 2007 |
| Journal | J Clin Invest | Volume | 117 |
| Issue | 5 | Pages | 1361-9 |
| PubMed ID | 17446931 | Mgi Jnum | J:122114 |
| Mgi Id | MGI:3713183 | Doi | 10.1172/JCI29470 |
| Citation | Harbers SO, et al. (2007) Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. J Clin Invest 117(5):1361-9 |
| abstractText | We have developed a model of autoimmunity to investigate autoantibody-mediated cross-presentation of self antigen. RIP-mOVA mice, expressing OVA in pancreatic beta cells, develop severe autoimmune diabetes when given OT-I cells (OVA-specific CD8(+) T cells) and anti-OVA IgG but not when given T cells alone. Anti-OVA IgG is not directly injurious to the islets but rather enhances cross-presentation of apoptotic islet antigen to the OT-I cells, leading to their differentiation into potent effector cells. Antibody-driven effector T cell activation is dependent on the presence of activating Fc receptors for IgG (FcgammaRs) and cross-priming DCs. As a consequence, diabetes incidence and severity was reduced in mice lacking activating FcgammaRs. An intact complement pathway was also required for disease development, as C3 deficiency was also partially protective. C3-deficient animals exhibited augmented T cell priming overall, indicating a proinflammatory role for complement activation after the T cell priming phase. Thus, we show that autoreactive antibody can potently enhance the activation of effector T cells in response to cross-presented self antigen, thereby contributing to T cell-mediated autoimmunity. |
