CD8+ T cells from HIV-exposed but uninfected individuals suppress HIV activity

CD8 T cells from individuals who remain uninfected despite being repeatedly exposed to HIV-1 (known as exposed-uninfected or EU) exert strong HIV-suppressive activity, according to researchers at the San Raffaele Scientific Institute in Milan.

Dr Lucinda Furci and colleagues studied the CD8 T lymphocytes from a well-characterised cohort of 16 HIV-1-discordant monogamous heterosexual couples. The lymphocytes were tested for their suppressive activity against HIV-1 strains displaying different coreceptor usage (one using coreceptor R5, one using X4, and one using both 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.

The researchers report in the journal AIDS of 3 May that 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 four 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,” Dr Furci and colleagues write.

They conclude: “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.