Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation.
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.
Xiao
Zhengguo
Z
Center for Immunology and 2Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN 55455.
Mescher
Matthew F
MF
Jameson
Stephen C
SC
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008089:Listeria monocytogenes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics; D014616:Vaccinia virus / Q000276:immunology
D016827:CD8 Antigens; D010047:Ovalbumin