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© The Rockefeller University Press, 0022-1007/1997/9/859/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 6, September 15, 1997 859-865


Articles

Rapid Effector Function in CD8+ Memory T Cells

Ajit Lalvani, Roger Brookes, Sophie Hambleton, Warwick J. Britton, Adrian V.S. Hill, and Andrew J. McMichael

From the Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom

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.


Address correspondence to Ajit Lalvani, Nuffield Department of Clinical Medicine, University of Oxford, Level 7, John Radcliffe Hospital, Oxford OX3 9DU, UK. Phone: 44-1865-222301; FAX: 44-1865-222301; E-mail: ajit.lalvani{at}ndm.ox.ac.uk

1 Abbreviations used in this paper: ELISPOT, enzyme-linked immunospot; LDA, limiting dilution analysis; NP, nucleoprotein; SFC, spot-forming cell.


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