Antigen controls IL-7R alpha expression levels on CD8 T cells during full activation or tolerance induction.
The high-affinity chain of the IL-7 receptor, IL-7Ralpha (CD127), is expressed by effector CD8 T cells that have the capacity to become memory cells. IL-7Ralpha expression is uniformly high on naive CD8 T cells, and the majority of these cells down-regulate expression upon antigenic challenge. At the peak of expansion, the fraction of effectors expressing high IL-7Ralpha varies depending on the response examined. The signals that a CD8 T cell receives during a response to Ag that lead to altered expression of IL-7Ralpha have not been fully defined. In vitro experiments demonstrated that Ag alone is sufficient to down-regulate IL-7Ralpha on all cells and most of the cells rapidly re-express the receptor upon removal from Ag. Expression was not altered by the B7.1 costimulatory ligand or when IL-12 was present to provide the signal needed for development of effector functions, indicating that TCR engagement is sufficient to regulate IL-7Ralpha expression. Consistent with this, in vivo priming with peptide Ag resulted in IL-7Ralpha expression that inversely correlated with Ag levels, and expression levels were not changed when IL-12 or adjuvant were administered with Ag. A large fraction of the cells present at the peak of expansion had re-expressed IL-7Ralpha, but most of these cells failed to survive; those that did survive expressed high IL-7Ralpha levels. Thus, Ag-dependent signals regulate IL-7Ralpha levels on responding CD8 T cells, and this occurs whether the responding cells become fully activated or are rendered tolerant by administration of peptide Ag alone.
Hammerbeck
Christopher D
CD
Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
Mescher
Matthew F
MF
D000818:Animals; D000941:Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D002478:Cells, Cultured; D002999:Clone Cells; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004527:Egg Proteins / Q000502:physiology; D007108:Immune Tolerance / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D008089:Listeria monocytogenes / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000502:physiology; D010446:Peptide Fragments; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D015203:Reproducibility of Results; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology
D000941:Antigens; D004527:Egg Proteins; C110366:OVA-8; D010446:Peptide Fragments; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D010047:Ovalbumin