Non-cytotoxic inhibition of HIV-1 infection by unstimulated CD8+ T lymphocytes from HIV-exposed-uninfected individuals

Lucinda Furci, Lucia Lopalco, Patrizia Loverro, Marina Sinnone, Giuseppe Tambussi, Adriano Lazzarin, Paolo Lusso

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Some individuals remain uninfected despite repeated exposure to HIV-1 [exposed-uninfected (EU)]. In addition to genetic factors, acquired immune responses elicited by repeated exposure to HIV antigens may contribute to protection. We investigated the ability of unstimulated CD8+ T lymphocytes from EU individuals to inhibit HIV-1 infection. Methods: Peripheral blood CD8+ T lymphocytes from a well-characterized cohort of 16 HIV-1-discordant monogamous heterosexual couples were tested for their suppressive activity against HIV-1 strains displaying different coreceptor usage (R5, X4, X4R5). To evaluate the in vivo functional competence of CD8+ T cells, no ex vivo activatory stimuli were used prior to cocultivation with infected CD4+ T cells. In some experiments, a semi-permeable membrane was used to separate CD4+ and CD8+ T cells. Results: Unstimulated CD8+ T cells from all but one of the EU individuals analysed effectively inhibited the growth of all HIV-1 strains, regardless of their coreceptor usage, with a mean potency similar to that of asymptomatic HIV-infected patients. The HIV-inhibitory activity persisted for a long time after ceasing high-risk sexual behaviour, although a moderate decline was observed starting 4 years after the last risk episode. Transwell culture experiments showed that soluble factors are involved in CD8-mediated viral suppression, although the activity was higher when cell-to-cell contact was allowed. Conclusions: These data demonstrate that CD8+ T cells from EU individuals exert a strong, broad-spectrum HIV-suppressive activity, suggesting a role of non-cytotoxic antiviral mechanisms in resistance to HIV-1 infection.

Original languageEnglish
Pages (from-to)1003-1008
Number of pages6
JournalAIDS (London, England)
Volume16
Issue number7
DOIs
Publication statusPublished - May 3 2002

Keywords

  • Chemokines
  • HIV-1 resistance
  • Natural immunity
  • Sexual behaviour
  • Viral coreceptors

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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