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.
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-infectedpatients. 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.
Authors: Holly Janes; Lawrence Corey; Gita Ramjee; Lindsay N Carpp; Carl Lombard; Myron S Cohen; Peter B Gilbert; Glenda E Gray Journal: AIDS Res Hum Retroviruses Date: 2018-06-19 Impact factor: 2.205
Authors: A L Erickson; C B Willberg; V McMahan; A Liu; S P Buchbinder; L A Grohskopf; R M Grant; D F Nixon Journal: Clin Vaccine Immunol Date: 2008-09-24
Authors: Shameem Z Jaumdally; Anabela Picton; Caroline T Tiemessen; Maria Paximadis; Heather B Jaspan; Hoyam Gamieldien; Lindi Masson; David Coetzee; Anna-Lise Williamson; Francesca Little; Pamela P Gumbi; Jo-Ann S Passmore Journal: Immunology Date: 2017-05-24 Impact factor: 7.397