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The Journal of Immunology, 1999, 162: 7080-7087.
Copyright © 1999 by The American Association of Immunologists

Human Virus-Specific CD8+ CTL Clones Revert from CD45ROhigh to CD45RAhigh In Vivo: CD45RAhighCD8+ T Cells Comprise Both Naive and Memory Cells1

Mark R. Wills2, Andrew J. Carmichael2, Michael P. Weekes2, Kim Mynard, Georgina Okecha, Ray Hicks and J. G. Patrick Sissons

Department of Medicine, University of Cambridge Clinical School, Cambridge, United Kingdom

It has been generally believed that human CD8+ memory cells are principally found within the CD45ROhigh population. There are high frequencies of CD8+ memory CTL specific for the human CMV tegument phosphoprotein pp65 in PBMC of long-term virus carriers; the large population of memory CTL specific for a given pp65 peptide contains individual CTL clones that have greatly expanded. In this study, we found high frequencies of pp65 peptide-specific memory CTL precursors in the CD45ROhighCD45RA- population, but also appreciable frequencies in the CD45RAhigh subpopulation. Because the majority of CD8+ T cells in PBMC are CD45RAhigh, more of the total pp65-specific memory CTL pool is within the CD45RAhigh than in the CD45ROhigh compartment. Using clonotypic oligonucleotide probes to quantify the size of individual pp65-specific CTL clones in vivo, we found the CD45RAhigh population contributed 6- to 10-fold more than the CD45ROhigh population to the total virus-specific clone size in CD8+ cells. During primary CMV infection, an individual virus-specific CTL clone was initially CD45ROhigh, but after resolution of infection this clone was detected in both the CD45ROhigh and the CD45RAhigh populations. We conclude that CD45RA+ human CD8+ T cells do not solely comprise naive cells, but contain a very significant proportion of memory cells, which can revert from the CD45ROhigh to CD45RAhigh phenotype in vivo.




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