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

AIDS. 2002 May 3;16(7):1003-8. doi: 10.1097/00002030-200205030-00006.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Dose-Response Relationship, Immunologic
  • Environmental Exposure
  • Female
  • HIV Infections / immunology*
  • HIV Seronegativity / immunology*
  • HIV-1 / classification
  • HIV-1 / physiology*
  • Humans
  • Immunity, Cellular
  • Immunity, Innate
  • Lymphocyte Subsets / immunology*
  • Male
  • Receptors, HIV / classification
  • Risk-Taking
  • Sexual Behavior
  • Sexual Partners
  • Species Specificity

Substances

  • Receptors, HIV