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

Zhengguo Xiao, Matthew F. Mescher, Stephen C. Jameson

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


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. JEM

Original languageEnglish (US)
Pages (from-to)2667-2677
Number of pages11
JournalJournal of Experimental Medicine
Issue number11
StatePublished - Oct 29 2007

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