First Author | Spielman J | Year | 1998 |
Journal | J Immunol | Volume | 161 |
Issue | 12 | Pages | 7063-70 |
PubMed ID | 9862744 | Mgi Jnum | J:112121 |
Mgi Id | MGI:3655560 | Doi | 10.4049/jimmunol.161.12.7063 |
Citation | Spielman J, et al. (1998) Perforin/Fas-ligand double deficiency is associated with macrophage expansion and severe pancreatitis. J Immunol 161(12):7063-70 |
abstractText | We report that perforin/Fas-ligand double-deficient mice die early of severe pancreatitis. Female mice, in addition, are infertile and suffer from hysterosalpingitis. Tissue destruction is accompanied by infiltration with Mac-1 (CD11b)-positive monocytes/macrophages, Mac-1-positive T cells, and expansion of CD8+ T cells. In vivo inactivation of monocytes/macrophages by carrageenan reverses disease progression and restores fertility of female mice. Perforin/Fas-ligand double-deficient CD4+ or CD8+ CTL are unable to lyse cognate-activated macrophages, and therefore are unable to mediate negative feedback regulation by lysis of APCs, thereby preventing further T cell activation. These studies demonstrate a novel role for perforin in homeostatic regulation of the immune response. |