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Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation.

ABSTRACT: CD8 is critical for T cell recognition of peptide/class I major histocompatability complex ligands, yet is down-regulated during activation of CD8 T cells. We report that loss of CD8 expression early during in vivo responses to vaccinia virus or Listeria monocytogenes (LM) correlates with decreased T cell staining with specific class I/peptide tetramers and reduced CD8 T cell sensitivity for antigen. Loss of CD8 cell surface expression occurs despite sustained mRNA expression, and CD8 levels return to normal levels during differentiation of memory cells, indicating a transient effect. We determined that during response to LM, CD8 down-regulation is regulated by T cell reactivity to type I interferon (IFN-I) because CD8 loss was averted on IFN-I receptor-deficient T cells. IFN-I alone was not sufficient to drive CD8 down-regulation, however, as antigen was also required for CD8 loss. These results suggest that CD8 effector T cell differentiation involves a transient down-regulation of antigen sensitivity (CTL "detuning"), via reduced CD8 expression, a feature that may focus the effector response on target cells expressing high levels of antigen (e.g., infected cells), while limiting collateral damage to bystander cells.

SUBMITTER: Xiao Z

PROVIDER: S-EPMC2118473 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation.

Xiao Zhengguo Z Mescher Matthew F MF Jameson Stephen C SC

The Journal of experimental medicine 20071022 11

CD8 is critical for T cell recognition of peptide/class I major histocompatability complex ligands, yet is down-regulated during activation of CD8 T cells. We report that loss of CD8 expression early during in vivo responses to vaccinia virus or Listeria monocytogenes (LM) correlates with decreased T cell staining with specific class I/peptide tetramers and reduced CD8 T cell sensitivity for antigen. Loss of CD8 cell surface expression occurs despite sustained mRNA expression, and CD8 levels ret ...[more]

PMID: 17954566

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Dataset Information

Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation.

Publications

Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation.

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