Large HIV-specific CD8 cytotoxic T-lymphocyte (CTL) clones reduce their overall size but maintain high frequencies of memory CTL following highly active antiretroviral therapy.

Immunology
Michael P WeekesAndrew J Carmichael

Abstract

Cytotoxic T-lymphocytes (CTL) play an important role in the control of human immunodeficiency virus (HIV) and of human cytomegalovirus (HCMV) infection. Following highly active antiretroviral therapy (HAART), most studies have demonstrated a decline in the frequency of HIV-specific CTL. We analysed the effect of HAART on the size, phenotype and function of individual HIV- and HCMV-specific CTL clones, using clonotypic oligonucleotide probing specific for the T-cell receptor (TCR) beta-chain hypervariable sequence of defined immunodominant CTL clones specific for peptides of HIV or HCMV, and quantified the limiting dilution analysis frequencies of CTL precursors (CTLp) specific for the same viral peptides. We found that the clonal composition of CD8+ T cells specific for HIV gag and env epitopes was highly focused and did not change after HAART. Following HAART, there was progressive contraction of HIV-specific CD8+ clones, especially in the CD28- CD27- subpopulation--the remaining cells of contracting HIV-specific clones were predominantly CD28- CD27+ CD45RO(hi). We observed maintenance of strong functional HIV-specific CD8+ T-cell responses in limiting dilution analysis following HAART, indicating preferential loss of HIV-spec...Continue Reading

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May 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark R WillsAndrew J Carmichael
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Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jianhong CaoM Juliana McElrath
Oct 21, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael P WeekesAndrew J Carmichael

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Citations

Mar 31, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·David J H F KnappChanson J Brumme
Sep 11, 2007·Cellular Immunology·Tobias M NowackiMagdalena Tary-Lehmann
May 2, 2013·PLoS Pathogens·Leon C W LinDavid C Tscharke
Apr 30, 2009·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Melanie WieselAnnette Oxenius
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth K DayMark R Wills

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