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

First Author  Xiao Z Year  2007
Journal  J Exp Med Volume  204
Issue  11 Pages  2667-77
PubMed ID  17954566 Mgi Jnum  J:126126
Mgi Id  MGI:3760576 Doi  10.1084/jem.20062376
Citation  Xiao Z, et al. (2007) Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation. J Exp Med 204(11):2667-77
abstractText  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.
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