Journal of Virology, November 1999, p. 9153-9160, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

MRC Human Immunology Unit, Institute of
Molecular Medicine, Oxford OX3 9DS, United
Kingdom,1 and Department of Clinical
Viro-Immunology,
Received 23 February 1999/Accepted 23 July 1999
Few studies have examined longitudinal changes in human
immunodeficiency virus type 1 (HIV)-specific cytotoxic T lymphocytes (CTL). To more closely define the natural history of HIV-specific CTL,
we used HLA-peptide tetrameric complexes to study the longitudinal CD8+ T-cell response evolution in 16 A*0201-positive
untreated individuals followed clinically for up to 14 years. As early
as 1 to 2 years after seroconversion, we found a significant
association between high frequencies of A*0201-restricted
p17Gag/Pol tetramer-binding cells and slower disease
progression (P < 0.01). We observed that responses
could remain stable over many months, but any longitudinal changes that
occurred were typically accompanied by reciprocal changes in RNA viral
load. Phenotypic analysis with markers CD45RO, CD45RA, and CD27
identified distinct subsets of antigen-specific cells and the
preferential loss of CD27+ CD45RO+ cells during
periods of rapid decline in the frequency of tetramer-binding cells. In
addition we were unable to confirm previous studies showing a
consistent selective loss of HIV-specific cells in the context of
sustained Epstein-Barr virus-specific cell frequencies. Overall, these
data support a role of HIV-specific CTL in the control of disease
progression and suggest that the ultimate loss of such CTL may be
preferentially from the CD27+ CD45RO+ subset.
*
Corresponding author. Mailing address: MRC Human
Immunology Unit, Institute of Molecular Medicine, John Radcliffe
Hospital, Oxford OX3 9DS, United Kingdom. Phone: 01865-222334. Fax:
01865-222502. E-mail: gogg{at}worf.molbiol.ox.ac.uk.
Present address: TB Research Programme, Medical Research Council
Laboratories, Banjul, The Gambia.
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