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Impairment of non-muscle myosin IIA in human CD41 T cells contributes to functional deficits in the elderly

Cellular & Molecular Immunology 2012年第1期9卷 86-96页

作者： Stefania Cane Subramaniam Ponnappan Usha Ponnappan Department of Microbiology and Immunology University of Arkansas for Medical SciencesLittle RockARUSA Department of Geriatrics University of Arkansas for Medical SciencesLittle RockARUSA

Physiological aging imposes significant alterations in the repertoire of T cells and all associated *** several studies have reported defects upon antigen-induced activation of T cells during aging,the molecular mechanisms that control T-cell receptor(TCR)downmodulation remain to be fully *** previous studies have assessed the role of F-actin in regulating activation-induced TCR internalization,few have delineated the roles of motor proteins,such as non-muscle myosin IIA(nmmiia).In this study,we describe a series of experiments supporting the hypothesis that effective TCR downmodulation requires not only efficient reorganization of the actin cytoskeleton,but also functional *** the first time,we show that CD41 T cells from elderly human donors have dysfunctional nmmiia that contributes to delaying activation-induced TCR internalization and impairing calcium ***,our results demonstrate that chemical inhibition of nmmiia in CD41 T cells from young donors also results in complete abrogation of TCR internalization,strongly supporting the fundamental role of nmmiia in modulating this *** observations that the generation of an efficient T-cell response requires migration prompted us to investigate whether nmmiia also plays a regulatory role in CD41 T-cell *** show that chemical inhibition of nmmiia downmodulates chemotactic migration in CD41 T cells from both young and elderly ***,these data demonstrate a significant contribution of dysfunctional nmmiia to TCR-mediated functional defects during aging.

关键词： chemotaxis Hsp90 immune senescence nmmiia TCR internalization

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