High levels of human immunodeficiency virus infection of CD8 lymphocytes expressing CD4 in vivo

Alexandra Cochrane, Stuart Imlach, Clifford Leen, Gordon Scott, Dermot Kennedy, Peter Simmonds

Research output: Contribution to journalArticlepeer-review

Abstract

Human immunodeficiency virus (HIV)-infected CD8 lymphocytes have been reported in vivo, but the mechanism of infection remains unclear. Experiments using the thy/hu mouse model support export of intrathymically infected CD8 precursors, while recent in vitro data suggest that mature CD8 lymphocytes upregulate CD4 upon activation (generating a CD8bright CD4dim phenotype) and are susceptible to HIV infection. To determine whether these mechanisms operate in vivo and to assess their relative importance in the generation of circulating HIV-infected CD8 lymphocytes, we quantified HIV long terminal repeat (LTR) DNA in CD8+ CD4- and CD8bright CD4dim lymphocytes isolated from HIV-infected individuals by fluorescence-activated cell sorting. HIV infection of CD8 lymphocytes was demonstrated in 17 of 19 subjects, with a significant inverse relationship between level of infection and CD4 lymphocyte count (R = -0.73; P <0.001). The level of HIV infection of CD8bright CD4dim lymphocytes was significantly higher (median, 1,730 HIV LTR copies/10(6) cells; n = 9) than that of CD8+ CD4- lymphocytes (undetectable in seven of nine individuals; P <0.01) and approached that of CD4 lymphocytes from the same individuals (median, 3,660 HIV LTR copies/10(6) cells). CD8bright CD4dim lymphocytes represented 0.8 to 3.3% of total CD8 lymphocytes and were most prevalent in the memory subset. Thus, HIV-infected CD8 lymphocytes commonly circulate in HIV-infected individuals and are generated through infection of activated CD8 lymphocytes rather than through export of intrathymically infected precursors. The high level of infection of CD8bright CD4dim lymphocytes could have a direct role in the decline in CD8 lymphocyte function that accompanies HIV disease progression.
Original languageEnglish
Pages (from-to)9862-71
Number of pages10
JournalJournal of Virology
Volume78
Issue number18
DOIs
Publication statusPublished - Sep 2004

Keywords

  • Adult
  • Antigens, CD4
  • Base Sequence
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • DNA, Viral
  • HIV
  • HIV Infections
  • HIV Long Terminal Repeat
  • Humans
  • Middle Aged
  • Models, Biological
  • Phenotype
  • T-Lymphocyte Subsets

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