HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, H.-J. Articles by Nel, A. E. Search for Related Content PubMed PubMed Citation Articles by Kim, H.-J. Articles by Nel, A. E.

The Role of Phase II Antioxidant Enzymes in Protecting Memory T Cells from Spontaneous Apoptosis in Young and Old Mice¹

Division of Clinical Immunology and Allergy, Department of Medicine, University of California, Los Angeles, CA 90095

Aging is associated with a functional decline and change in the phenotypic distribution of T cell subsets. The free radical theory of aging is widely promoted as the mechanistic basis for cellular senescence, including the immune system. Although the exact molecular explanation for the role of oxidative stress in cellular senescence is unclear, there is a connection to altered mitochondrial function, both as a contributor and as a target of oxidative stress. In this study we demonstrate that splenic T lymphocytes from old C57BL/6 mice exhibit a significant decline in mitochondrial membrane potential (_m). However, despite this change, there is a lower rate of withdrawal apoptosis in the memory CD4⁺ and CD8⁺ T cells. To explain the survival of these long-lived cells against a background of increased oxidative stress, we demonstrate increased glutathione production and phase II enzyme expression, which combine to protect memory T cells against oxidative stress, mitochondrial dysfunction, and cell death. The accumulation of memory T cells with aging explains higher phase II enzyme expression in CD4⁺ and CD8⁺ T cells from old mice. Compared with wild-type mice, mice lacking the expression of NF-E2-related factor-2, the transcription factor that regulates phase II enzyme expression, had a significantly enhanced rate of apoptosis in the presence of an oxidative stress stimulus. NF-E2-related factor-2-deficient T cells exhibit a bigger decline in _m and increased reactive oxygen species production than cells from wild-type animals. Taken together, we suggest that phase II enzyme expression and the accompanying increase in intracellular thiol levels protect memory T cells from mitochondrial dysfunction and spontaneous apoptosis.

This article has been cited by other articles:

				A. J. Ross, L. A. Dailey, L. E. Brighton, and R. B. Devlin Transcriptional Profiling of Mucociliary Differentiation in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 169 - 185. [Abstract] [Full Text] [PDF]

				M. G. Marko, T. Ahmed, S. C. Bunnell, D. Wu, H. Chung, B. T. Huber, and S. N. Meydani Age-Associated Decline in Effective Immune Synapse Formation of CD4+ T Cells Is Reversed by Vitamin E Supplementation J. Immunol., February 1, 2007; 178(3): 1443 - 1449. [Abstract] [Full Text] [PDF]