| First Author | Kägi D | Year | 1997 |
| Journal | J Exp Med | Volume | 186 |
| Issue | 7 | Pages | 989-97 |
| PubMed ID | 9314549 | Mgi Jnum | J:43468 |
| Mgi Id | MGI:1097769 | Doi | 10.1084/jem.186.7.989 |
| Citation | Kagi D, et al. (1997) Reduced incidence and delayed onset of diabetes in perforin-deficient nonobese diabetic mice. J Exp Med 186(7):989-97 |
| abstractText | To investigate the role of T cell-mediated, perforin-dependent cytotoxicity in autoimmune diabetes, perforin-deficient mice were backcrossed with the nonobese diabetes mouse strain. It was found that the incidence of spontaneous diabetes over a 1 yr period was reduced from 77% in perforin +/+ control to 16% in perforin-deficient mice. Also, the disease onset was markedly delayed (median onset of 39.5 versus 19 wk) in the latter. Insulitis with infiltration of CD4(+) and CD8(+) T cells occurred similarly in both groups of animals. Lower incidence and delayed disease onset were also evident in perforin-deficient mice when diabetes was induced by cyclophosphamide injection. Thus, perforin-dependent cytotoxicity is a crucial effector mechanism for beta cell elimination by cytotoxic T cells in autoimmune diabetes. However, in the absence of perforin chronic inflammation of the islets can lead to diabetogenic beta cell loss by less efficient secondary effector mechanisms. |
