Published online
doi:10.1084/jem.20062376
The Journal of Experimental Medicine, Vol. 204, No. 11, 2667-2677
The Rockefeller University Press, 0022-1007 $30.00
© Xiao et al.
Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation
Zhengguo Xiao1,2,
Matthew F. Mescher1,2, and
Stephen C. Jameson1,2
1 Center for Immunology and 2 Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN 55455
CORRESPONDENCE Stephen C. Jameson: james024{at}umn.edu
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.
Abbreviations used: DKO, double KO; LM, Listeria monocytogenes; MFI, mean fluorescence intensity; VV, vaccinia virus.
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