Abstract
During HIV infection, specific responses exhibited by CD8+ T cells are crucial to establish an early, effective, and sustained viral control, preventing severe immune alterations and organ dysfunction. Several CD8+ T cells subsets have been identified, exhibiting differences in terms of activation, functional profile, and ability to limit HIV replication. Some of the most important CD8+ T cells subsets associated with viral control, production of potent antiviral molecules, and strong polyfunctional responses include Th1-like cytokine pattern and Tc17 cells. In addition, the expression of specific activation markers has been also associated with a more effective response of CD8+ T cells, as evidenced in HLA-DR+ CD38− cells. CD8+ T cells in both, peripheral blood and gut mucosa, are particularly important in individuals with a resistant phenotype, including HIV-exposed seronegative individuals (HESNs), long-term non-progressors (LTNPs) and HIV-controllers. Although the role of CD8+ T cells has been extensively explored in the context of an established HIV-1 infection, the presence of HIV-specific cells with effector abilities and a defined functional profile in HESNs, remain poorly understood. Here, we reviewed studies carried out on different subpopulations of CD8+ T cells in relation with natural resistance to HIV infection and progression.
Highlights
HIV infection is currently one of the most important health problems worldwide; continuous exposure to the virus may result in infection, an interesting group of repeatedly exposed individuals known as HIV-exposed seronegative individuals (HESNs), who do not exhibit any clinical or serological evidence of HIV infection, has been described [1, 2]
Among those who acquire the infection, different patterns of AIDS progression are observed: most infected patients progress to AIDS after 8–10 years, but some uncommon patients, known as long-term non-progressors (LTNPs), remain asymptomatic for more than 10 years, exhibiting low viral loads in the absence of antiretroviral therapy [3]
Regarding the functional ability of CD8+ T cells found in HESNs, several cohorts of HESNs have been reported to exhibit HIV-specific CD8+ T cells secreting IFN-γ and IL-2 [105, 109, 110]
Summary
HIV infection is currently one of the most important health problems worldwide; continuous exposure to the virus may result in infection, an interesting group of repeatedly exposed individuals known as HIV-exposed seronegative individuals (HESNs), who do not exhibit any clinical or serological evidence of HIV infection, has been described [1, 2]. This phenotype is characterized by low cytotoxicity and cytokines production. Regarding the functional ability of CD8+ T cells found in HESNs, several cohorts of HESNs have been reported to exhibit HIV-specific CD8+ T cells secreting IFN-γ and IL-2 [105, 109, 110] These cells exhibit high activity against the virus, with the production of increased levels of perforin and granzyme B, and both responses were negatively correlated with the time of the last unprotected sexual exposure, suggesting that they could have played a crucial role in avoiding the establishment of the infection [104]. These results suggest that if the HESNs do acquire the infection, they probably become controllers; this remains to be elucidated
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