Distinct CD3 + CD14 + T Cell-Monocytes are dynamic complexes that harbor HIV and are increased with glucose intolerance.
Distinct CD3 + CD14 + T Cell-Monocytes are dynamic complexes that harbor HIV and are increased with glucose intolerance.
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独特的 CD3 CD14 T 细胞-单核细胞是携带 HIV 的动态复合物，并随着葡萄糖不耐受而增加。
DOI：
10.1101/2023.04.24.538020
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Gangula,Ram
中科院分区：
文献类型：
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作者：
Wanjalla,CelestineN;Simmons,Joshua;Oakes,Jared;Zhang,Xiuqi;Nochowicz,Cindy;Priest,Stephen;Bailin,SamuelS;Warren,ChristopherM;Mashayekhi,Mona;Beasley,HeatherK;Wang,Jian;Meenderink,Leslie;Sheng,Quanhu;Stolze,Joey;Gangula,Ram
心脏代谢疾病的风险增加伴随持续的全身炎症。然而，先天性和适应性免疫系统的功能在人谁发展这些条件仍然很难定义。双联体或细胞-细胞复合物通常从流式细胞术和其他免疫表型分析中排除，这限制了我们对它们与疾病状态关系的理解。使用充分表征的临床队列，包括受控制的HIV参与者作为慢性炎症和增加的免疫细胞相互作用的模型，我们表明，与CD 3 + T细胞复合的循环CD 14+单核细胞是动态的，生物学相关的，并且在调整混杂因素后糖尿病患者中增加。复合物形成功能性免疫突触，增加促炎细胞因子的表达和更大的葡萄糖利用。此外，在HIV感染者中，CD 3 + T细胞：CD 14+单核细胞复合物与单独的匹配的CD 14+单核细胞或CD 4 + T细胞相比具有更多的HIV拷贝。我们的研究结果表明，循环中的CD 3 + T细胞：CD 14+单核细胞对代表动态的细胞相互作用，可能有助于炎症和心脏代谢疾病的发病机制，并可能起源或维持，部分，慢性病毒感染。这些发现为未来研究T细胞-单核细胞-细胞复合物与免疫介导疾病（包括HIV和糖尿病）的关系奠定了基础。
An increased risk of cardiometabolic disease accompanies persistent systemic inflammation. Yet, the innate and adaptive immune system features in persons who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled HIV as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14+ monocytes complexed to CD3+ T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3+T-cell: CD14+monocyte complexes had more HIV copies compared to matched CD14+ monocytes or CD4+ T cells alone. Our results demonstrate that circulating CD3+T-cell:CD14+monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis and may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cellmonocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes.