Non-cytotoxic inhibition of HIV-1 infection by unstimulated CD8+ T lymphocytes from HIV-exposed-uninfected individuals.
OBJECTIVE
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.
Furci
Lucinda
L
Unit of Human Virology, DIBIT, San Raffaele Scientific Institute, Via Olgettina n. 58, Milan 20132, Italy. lucinda.furci@hsr.it
Lopalco
Lucia
L
Loverro
Patrizia
P
Sinnone
Marina
M
Tambussi
Giuseppe
G
Lazzarin
Adriano
A
Lusso
Paolo
P
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D004306:Dose-Response Relationship, Immunologic; D004781:Environmental Exposure; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D015728:Receptors, HIV / Q000145:classification; D012309:Risk-Taking; D012725:Sexual Behavior; D012747:Sexual Partners; D013045:Species Specificity
D015728:Receptors, HIV