IFN-gamma receptor-deficient mice are hypersensitive to the anti-CD3-induced cytokine release syndrome and thymocyte apoptosis. Protective role of endogenous nitric oxide.

摘要: Mice with a disruption of the IFN-gamma receptor alpha-chain gene (IFN-gamma R alpha o/o mice) were found to be significantly more sensitive than their wild-type counterparts induction anti-CD3-induced disease syndrome. Specifically, when given selected dose anti-CD3 Ab, mice developed severe hypothermia and hypoglycemia, leading 100% mortality within 72 h. In contrast, failed develop overt pathologic manifestations survived. Histologic examination revealed apoptosis in thymuses spleens, which pronounced mutant mice, as confirmed by flow cytometric DNA electrophoretic analysis. Apoptosis affected mainly CD4+CD8+ CD4+CD8- thymocytes. Other histologic alterations steatosis livers, erythrocyte extravasation infiltration apoptotic cells lungs, all exclusively observed mice. Blood levels TNF, IL-2, IL-6, IL-10 slightly elevated but insufficiently so explain increased severity. Thus, even cytokine receiving high doses Ab not associated morbidity or apoptosis. barely detectable anti-CD3-challenged relatively Increased susceptibility was impaired nitric oxide (NO) production, indicated lower plasma nitrite transient expression spleen inducible NO synthase mRNA. Moreover, treatment inhibitor N-nitro-L-arginine methylester resulted mortality. The data indicate that produce less are therefore deleterious effect Ab.