Cytokine-dependent regulation of NADPH oxidase activity and the consequences for activated T cell homeostasis

Purushothaman, Divya ; Sarin, Apurva (2009) Cytokine-dependent regulation of NADPH oxidase activity and the consequences for activated T cell homeostasis Journal of Experimental Medicine, 206 (7). pp. 1515-1523. ISSN 0022-1007

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Official URL: http://jem.rupress.org/content/206/7/1515.short

Related URL: http://dx.doi.org/10.1084/jem.20082851

Abstract

Cellular dependence on growth factors for survival is developmentally programmed and continues in adult metazoans. Antigen-activated T cell apoptosis in the waning phase of the immune response is thought to be triggered by depletion of cytokines from the microenvironment. T cell apoptosis resulting from cytokine deprivation is mediated by reactive oxygen species (ROS), but their source and position in the apoptotic cascade is poorly understood. RNA interference approaches implicated the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in neglect-induced apoptosis in T cells. Using mice deficient for the catalytic subunit gp91phox to characterize the molecular link to activated T cell apoptosis, we show that gp91phox-deficient T (T-/-) cells generated mitochondrial superoxide but had diminished hydrogen peroxide production in response to neglect, which, in turn, regulated Jun N-terminal kinase-dependent Bax activation and apoptosis. Activated T-/- cells were distinguished by improved survival after activation by superantigens in vivo, adoptive transfers into congenic hosts, and higher recall responses after immunization. Thus, the NADPH oxidase may regulate adaptive immunity in addition to its previously well-characterized role in the innate response.

Item Type:Article
Source:Copyright of this article belongs to Rockefeller University Press.
ID Code:62119
Deposited On:17 Sep 2011 11:43
Last Modified:17 Sep 2011 11:43

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