Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
J Med Virol. 2022 Jul;94(7):3043-3053. doi: 10.1002/jmv.27696. Epub 2022 Mar 12.
Human immunodeficiency virus type 1 (HIV-1) infection causes considerable morbidity and mortality worldwide. Although antiretroviral therapy (ART) has largely transformed HIV infection from a fatal disease to a chronic condition, approximately 10%-40% of HIV-infected individuals who receive effective ART and sustain long-term viral suppression still cannot achieve optimal immune reconstitution. These patients are called immunological nonresponders, a state associated with poor clinical prognosis. Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved unconventional T-cell subset defined by expression of semi-invariant αβ T-cell receptor (TCR), which recognizes metabolites derived from the riboflavin biosynthetic pathway presented on major histocompatibility complex-related protein-1. MAIT cells, which are considered to act as a bridge between innate and adaptive immunity, produce a wide range of cytokines and cytotoxic molecules upon activation through TCR-dependent and TCR-independent mechanisms, which is of major importance in defense against a variety of pathogens. In addition, MAIT cells are involved in autoimmune and immune-mediated diseases. The number of MAIT cells is dramatically and irreversibly decreased in the early stage of HIV infection and is not fully restored even after long-term suppressive ART. In light of the important role of MAIT cells in mucosal immunity and because microbial translocation is inversely associated with CD4 T-cell counts, we propose that MAIT cells participate in the maintenance of intestinal barrier integrity and microbial homeostasis, thus further affecting immune reconstitution in HIV-infected individuals.
人类免疫缺陷病毒 1 型（HIV-1）感染在全球范围内造成了相当大的发病率和死亡率。尽管抗逆转录病毒疗法（ART）在很大程度上将 HIV 感染从致命疾病转变为慢性疾病，但大约 10%-40%接受有效 ART 并长期抑制病毒的 HIV 感染者仍无法实现最佳免疫重建。这些患者被称为免疫无应答者，处于与不良临床预后相关的状态。黏膜相关不变 T（MAIT）细胞是一种进化上保守的非常规 T 细胞亚群，其特征是表达半不变的αβ T 细胞受体（TCR），该受体识别来自核黄素生物合成途径的代谢物，呈现在主要组织相容性复合体相关蛋白-1 上。MAIT 细胞被认为是先天免疫和适应性免疫之间的桥梁，通过 TCR 依赖性和 TCR 非依赖性机制激活后产生广泛的细胞因子和细胞毒性分子，这对于防御各种病原体至关重要。此外，MAIT 细胞参与自身免疫和免疫介导的疾病。在 HIV 感染的早期阶段，MAIT 细胞的数量急剧且不可逆转地减少，即使在长期抑制性 ART 后也无法完全恢复。鉴于 MAIT 细胞在黏膜免疫中的重要作用，并且微生物易位与 CD4 T 细胞计数呈负相关，我们提出 MAIT 细胞参与维持肠道屏障完整性和微生物动态平衡，从而进一步影响 HIV 感染者的免疫重建。
