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Differential Sensitivity of Naïve and Memory Subsets of Human CD8+ T Cells to TNF-α-Induced Apoptosis

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In this investigation, we have examined the relative sensitivity of human naïve, central memory (TCM), and two types of effector memory CD8+ T cells (TEM and TEMRA) to TNF-α-induced apoptosis. Our data show that naïve and TCM CD8+ T cells were sensitive, whereas TEM and TEMRA CD8+ T cells were relatively resistant to TNF-a-induced apoptosis. The apoptosis profile correlated with the activation of caspase-8 and caspase-3. However, no correlation was observed between relative sensitivity of four CD8 + T cell subsets to apoptosis and the expression of TNFR-I or TNFR-II. TEM and TEMRA CD8+ T cells displayed increased phosphorylation of IKKα/β and IκB and increased NF-κB activity as compared to naïve and TCM CD8+ T cells. Bcl-2, Bcl-xL and FLIPL expression was higher and Bax expression was lower in TEM and TEMRA CD8+ T cells as compared to naïve and TCM CD8+ T cells. These data suggest that signaling molecules downstream of TNFRs may be responsible for differential sensitivity among subsets of CD8+ T cells to TNF-α-induced apoptosis.

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Abbreviations

IAPs:

inhibitor of apoptosis proteins

TNF-α:

tumor necrosis factor-α

TNFR-I and TNFR-II:

tumor necrosis factor I and II

TCM :

central memory T cells

TEM :

effector memory T cells

TEMRA :

effector memory CD45RA+ T cells

TRAF2:

TNFR-associated factor 2

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ACKNOWLEDGMENT

This work was supported in part by USPHS grant AG18313.

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Authors and Affiliations

  1. Division of Basic and Clinical Immunology, University of California, Irvine, California, USA

    Sudhir Gupta, Houfen Su, Ruifen Bi & Sastry Gollapudi

  2. University of California, Medical Sciences I, C-240, Irvine, California, 92697, USA

    Sudhir Gupta

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  1. Sudhir Gupta
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Correspondence to Sudhir Gupta.

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Gupta, S., Su, H., Bi, R. et al. Differential Sensitivity of Naïve and Memory Subsets of Human CD8+ T Cells to TNF-α-Induced Apoptosis. J Clin Immunol 26, 193–203 (2006). https://doi.org/10.1007/s10875-006-9019-1

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