Functional discrepancies in HIV-specific CD8+ T-lymphocyte populations are related to plasma virus load
- PMID: 12462336
- DOI: 10.1023/a:1020656300027
Functional discrepancies in HIV-specific CD8+ T-lymphocyte populations are related to plasma virus load
Abstract
The potent ability of current antiretroviral drug regimens to control human immunodeficiency Virus-1 (HIV-1) replication, in conjunction with the clinical practice of structured therapeutic interruptions, provides a system in which virus levels are manipulated during a persistent infection in humans. Here, we exploit this system to examine the impact of variable plasma virus load (pVL) on the functionality of HIV-specific CD8+ T-lymphocyte populations. Using both ELISpot methodology and intracellular cytokine staining for interferon (IFN)-gamma to assess functional status, together with fluorochrome-labeled peptide-major histocompatibility complex (pMHC) class I tetramer analysis to detect the physical presence of CD8+ T lymphocytes expressing cognate T-cell receptors (TCRs), we observed that the proportion of HIV-specific CD8+ T lymphocytes capable of mounting an effector response to antigen challenge directly ex vivo is related to the kinetics of virus exposure. Specifically, (a) after prolonged suppression of pVL with antiretroviral therapy (ART), physical and functional measures of HIV-specific CD8+ T-lymphocyte frequencies approximated; and (b) the percentage of functionally responsive cells in the HIV-specific CD8+ T lymphocyte populations declined substantially when therapy was discontinued and pVL recrudesced in the same patients. These results corroborate and extend observations in animal models that describe nonresponsive CD8+ T lymphocytes in the presence of high levels of antigen load and have implications for the interpretation of quantitative data generated by methods that rely on functional readouts.
Similar articles
-
Residual HIV-specific CD4 and CD8 T cell frequencies after prolonged antiretroviral therapy reflect pretreatment plasma virus load.AIDS. 2002 Nov 22;16(17):2317-22. doi: 10.1097/00002030-200211220-00012. AIDS. 2002. PMID: 12441804
-
Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load.Eur J Immunol. 2001 Apr;31(4):1115-21. doi: 10.1002/1521-4141(200104)31:4<1115::aid-immu1115>3.0.co;2-9. Eur J Immunol. 2001. PMID: 11298336
-
Functional restoration of human immunodeficiency virus and Epstein-Barr virus-specific CD8(+) T cells during highly active antiretroviral therapy is associated with an increase in CD4(+) T cells.Eur J Immunol. 2002 Apr;32(4):1080-9. doi: 10.1002/1521-4141(200204)32:4<1080::AID-IMMU1080>3.0.CO;2-R. Eur J Immunol. 2002. PMID: 11920575
-
Viral Inhibitory Activity of CD8+ T Cells in HIV Infection.AIDS Rev. 2019;21(3):115-125. doi: 10.24875/AIDSRev.19000068. AIDS Rev. 2019. PMID: 31532399 Review.
-
Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers.Rev Med Virol. 2001 Jan-Feb;11(1):11-22. doi: 10.1002/rmv.295. Rev Med Virol. 2001. PMID: 11241799 Review.
Cited by
-
Isolation of viable antigen-specific CD8+ T cells based on membrane-bound tumor necrosis factor (TNF)-α expression.J Immunol Methods. 2011 Jun 30;369(1-2):33-41. doi: 10.1016/j.jim.2011.04.003. Epub 2011 Apr 8. J Immunol Methods. 2011. PMID: 21501617 Free PMC article.
-
Tricks with tetramers: how to get the most from multimeric peptide-MHC.Immunology. 2009 Feb;126(2):147-64. doi: 10.1111/j.1365-2567.2008.02848.x. Immunology. 2009. PMID: 19125886 Free PMC article. Review.
-
Gain and loss of T cell subsets in old age--age-related reshaping of the T cell repertoire.J Clin Immunol. 2011 Apr;31(2):137-46. doi: 10.1007/s10875-010-9499-x. Epub 2011 Jan 18. J Clin Immunol. 2011. PMID: 21243520 Review.
-
Emergence of polyfunctional CD8+ T cells after prolonged suppression of human immunodeficiency virus replication by antiretroviral therapy.J Virol. 2008 Apr;82(7):3391-404. doi: 10.1128/JVI.02383-07. Epub 2008 Jan 16. J Virol. 2008. PMID: 18199637 Free PMC article.
-
Emerging concepts in the immunopathogenesis of AIDS.Annu Rev Med. 2009;60:471-84. doi: 10.1146/annurev.med.60.041807.123549. Annu Rev Med. 2009. PMID: 18947296 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials