| First Author | Kwan WH | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 6 | Pages | 2234-8 |
| PubMed ID | 22585573 | Mgi Jnum | J:190492 |
| Mgi Id | MGI:5448921 | Doi | 10.1172/JCI61019 |
| Citation | Kwan WH, et al. (2012) Antigen-presenting cell-derived complement modulates graft-versus-host disease. J Clin Invest 122(6):2234-8 |
| abstractText | Acute graft-versus-host disease (GvHD) is a serious complication of allogeneic hematopoietic cell transplantation (allo-HCT) that results from donor allogeneic T cell attack on host tissues. Based on previous work implicating immune cell-derived C3a and C5a as regulators of T cell immunity, we examined the effects of locally produced C3a and C5a on murine T cell-mediated GvHD. We found that total body irradiation, a conditioning regimen required to permit engraftment of allo-HCT, caused upregulation and activation of alternative pathway complement components by recipient APCs. Allo-HCT with decay accelerating factor-null (Daf1(-/-)) host BM and Daf1(-/-) donor lymphocytes led to exacerbated GvHD outcome and resulted in splenic and organ-infiltrating T cell expansion. T cells deficient in C3a receptor (C3aR) and/or C5a receptor (C5aR) responded weakly in allogeneic hosts and exhibited limited ability to induce GvHD. Using a clinically relevant treatment strategy, we showed that pharmacological C5aR blockade reduced GvHD morbidity. Our data mechanistically link APC-derived complement to T cell-mediated GvHD and support complement inhibition as a therapeutic strategy for GvHD in humans. |
