Rapid effector function in CD8+ memory T cells.
The nature of the CD8+ T cells that underlie antiviral protective immunological memory in vivo is unclear. We have characterized peptide-specific CD8+ T lymphocytes directly ex vivo from peripheral blood in humans with past exposure to influenza virus, using single cell interferon gamma (IFN-gamma) release as a measure of effector function. In individuals in the memory state with respect to influenza virus infection, unrestimulated antigen-specific CD8+ T cells displayed IFN-gamma release within 6 h of antigen contact, identifying a population of memory CD8+ T cells that exhibit effector function without needing to divide and differentiate over several days. We have quantified circulating CD8+ effector T cells specific for six different MHC class I-restricted influenza virus epitopes. Enumeration of these CD8+ T cells gives frequencies of peptide-specific T cells that correlate with, but are in general severalfold higher than, CTL precursor frequencies derived from limiting dilution analysis, indicating that this novel population of memory CD8+ T cells has hitherto been undetected by standard means. The phenotype of these cells, which persist at a low frequency long after recovery from an acute viral infection, suggests that they play a role in protective immunological memory.
Lalvani
A
A
Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. ajit.lalvani@ndm.ox.ac.uk
Brookes
R
R
Hambleton
S
S
Britton
W J
WJ
Hill
A V
AV
McMichael
A J
AJ
D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics; D006680:HLA Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007251:Influenza, Human / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma