Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals

Nichole R Klatt, Steven E Bosinger, Melicent Peck, Laura E Richert-Spuhler, Anke Heigele, Jillian P Gile, Nirav Patel, Jessica Taaffe, Boris Julg, David Camerini, Carlo Torti, Jeffrey N Martin, Steven G Deeks, Elizabeth Sinclair, Frederick M Hecht, Michael M Lederman, Mirko Paiardini, Frank Kirchhoff, Jason M Brenchley, Peter W HuntGuido Silvestri

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated ("putative progressors", PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = -0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.

Original languageEnglish (US)
Pages (from-to)e1004345
JournalPLoS pathogens
Volume10
Issue number8
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • CD4-Positive T-Lymphocytes/immunology
  • Cell Separation
  • DNA, Viral/analysis
  • Disease Progression
  • HIV Infections/immunology
  • Humans
  • Immunologic Memory/immunology
  • Immunophenotyping
  • Oligonucleotide Array Sequence Analysis
  • Stem Cells/immunology
  • T-Lymphocyte Subsets/immunology
  • Viral Load
  • Viremia/immunology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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  • Cite this

    Klatt, N. R., Bosinger, S. E., Peck, M., Richert-Spuhler, L. E., Heigele, A., Gile, J. P., Patel, N., Taaffe, J., Julg, B., Camerini, D., Torti, C., Martin, J. N., Deeks, S. G., Sinclair, E., Hecht, F. M., Lederman, M. M., Paiardini, M., Kirchhoff, F., Brenchley, J. M., ... Silvestri, G. (2014). Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals. PLoS pathogens, 10(8), e1004345. https://doi.org/10.1371/journal.ppat.1004345