Perforin/Fas-Ligand Double Deficiency Is Associated with Macrophage Expansion and Severe Pancreatitis
Copyright policy )Perforin/Fas-Ligand Double Deficiency Is Associated with Macrophage Expansion and Severe Pancreatitis
AbstractWe 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.
- Miami University United States
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Mice, Knockout, Antigen Presentation, Fas Ligand Protein, Membrane Glycoproteins, Macrophages, Macrophage-1 Antigen, CD8-Positive T-Lymphocytes, Macrophage Activation, Carrageenan, Lymphocyte Activation, Autoimmune Diseases, Feedback, Mice, Inbred C57BL, Mice, Animals, Female, Endometritis, Infertility, Female
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Mice, Knockout, Antigen Presentation, Fas Ligand Protein, Membrane Glycoproteins, Macrophages, Macrophage-1 Antigen, CD8-Positive T-Lymphocytes, Macrophage Activation, Carrageenan, Lymphocyte Activation, Autoimmune Diseases, Feedback, Mice, Inbred C57BL, Mice, Animals, Female, Endometritis, Infertility, Female
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