Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia.
Front Immunol. 2020 Sep 11;11:537044. doi: 10.3389/fimmu.2020.537044. eCollection 2020.
The HIV-exposed seronegative (HESN) status is for individuals who remain seronegative despite repeated exposure to HIV. One of the main cohorts within this group is men who have sex with men (MSM). Studies of this cohort have revealed different immunological and genetic mechanisms that can explain the phenomenon of natural HIV resistance. NK cells' higher effector capacity is related to natural resistance to HIV. Besides, a new population of NK cells with adaptive features was described recently. These cells are increased in some HESN cohorts and appear to be involved in better control of viral replication in primarily HIV-infected subjects. The present study evaluated the role of NK cells in the natural resistance to HIV-1 infection in MSM.
Phenotypic and functional features were evaluated in NK cells from two groups of MSM, at different risks of HIV infection, according to the number of sexual partners. The production of IFN-γ and β-chemokines was included in the analysis, as well as the cytotoxic capacity and adaptive NK cell frequency. Genetic features, such as HLA and KIR allele frequencies, were also explored.
High-risk MSM exhibit an increased frequency of fully mature and CD57/NKG2C NK cells. These individuals also show higher cytotoxic capacity and IFN-γ production in response to K562 stimuli. NK cells with a CD107a/IFN-γ functional profile were found more frequently and displayed higher IFN-γ production capacity among high-risk MSM than among low-risk MSM. The protective allele was only present in the high-risk MSM group as well as . The protective phenotype , in a homozygous state, was particularly abundant in the high-risk population. Notably, some of these functional features were related to higher frequencies of mature and CD57/NKG2C NK cells, which, in turn, were associated with a higher number of sexual partners.
The changes observed in the NK cell compartment can be driven by the magnitude of sexual exposure and immunological challenges of high-risk individuals, which could influence their resistance/susceptibility to HIV infection.
HIV 暴露但血清阴性（HESN）是指个体在反复接触 HIV 后仍保持血清阴性的状态。该群体中的主要队列之一是男男性行为者（MSM）。对该队列的研究揭示了不同的免疫和遗传机制，可以解释自然抵抗 HIV 的现象。NK 细胞更高的效应能力与自然抵抗 HIV 有关。此外，最近描述了一种具有适应性特征的新 NK 细胞群体。在一些 HESN 队列中，这些细胞增加，似乎参与了主要 HIV 感染者中病毒复制的更好控制。本研究评估了 NK 细胞在 MSM 对 HIV-1 感染的自然抵抗中的作用。
根据性伴侣数量，评估了两组 MSM 中 NK 细胞的表型和功能特征，这些 MSM 处于不同的 HIV 感染风险中。分析了 IFN-γ 和β趋化因子的产生，以及细胞毒性能力和适应性 NK 细胞频率。还探索了遗传特征，如 HLA 和 KIR 等位基因频率。
高风险 MSM 表现出更高频率的完全成熟和 CD57/NKG2C NK 细胞。这些个体对 K562 刺激也显示出更高的细胞毒性和 IFN-γ 产生能力。在高风险 MSM 中比在低风险 MSM 中发现了更多具有 CD107a/IFN-γ 功能特征的 NK 细胞，并且具有更高的 IFN-γ 产生能力。保护性等位基因 仅存在于高风险 MSM 组中， 也是如此。保护性表型 ，在纯合状态下，在高危人群中尤为丰富。值得注意的是，这些功能特征中的一些与成熟和 CD57/NKG2C NK 细胞的更高频率有关，而这些细胞又与更多的性伴侣数量有关。
NK 细胞区室中观察到的变化可能是由高风险个体的性暴露程度和免疫挑战驱动的，这可能影响他们对 HIV 感染的抵抗/易感性。
