Williams Dionna W, Flores Bianca R, Xu Yanxun, Wang Yuezhe, Yu Danyang, Peters Brandilyn A, Adedimeji Adebola, Wilson Tracey E, Merenstein Daniel, Tien Phyllis C, Cohen Mardge H, Weber Kathleen M, Adimora Adaora A, Ofotokun Igho, Fischl Margaret, Turan Janet, Turan Bülent, Laumet Geoffroy, Landay Alan L, Dastgheyb Raha M, Gange Stephen J, Weiser Sheri D, Rubin Leah H
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brain Behav Immun Health. 2022 Aug 29;25:100498. doi: 10.1016/j.bbih.2022.100498. eCollection 2022 Nov.
Neuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/<20cp/mL) enrolled in the Women's Interagency HIV Study completed neuropsychological testing and measures of depression (Center for Epidemiological Studies Depression Scale-CES-D), self-reported stress levels (Perceived Stress Scale-10), and post-traumatic stress (PTSD Checklist-Civilian Scale). Multiparametric flow cytometry evaluated T-cell activation state. Partial least squares regressions were used to examine T-cell phenotypes and neuropsychiatric outcome associations after confounder adjustment. In the total sample and among virally suppressed (VS)-WWH, CD4 T-cell exhaustion was associated with poorer learning and attention/working memory ('s < 0.05). In the total sample, CD4 T-cell activation was associated with better attention/working memory and CD8 T-cell co-stimulation and senescence was associated with poorer executive function ('s < 0.05). For mental health outcomes, in the total sample, CD4 T-cell activation was associated with more perceived stress and CD4 T-cell exhaustion was associated with less depressive symptoms ('s < 0.05). Among VS-WWH, CD4 senescence was associated with less perceive stress and CD8 T-cell co-stimulation and senescence was associated with higher depression ( < 0.05). Together, results suggest the contribution of peripheral CD4 and CD8 T-cell activation status to neuropsychiatric complications in WWH.
神经精神并发症在感染HIV的女性（WWH）中很常见。这些并发症背后的病理生理机制尚不完全清楚，但可能部分由免疫调节驱动。我们研究了有效免疫反应所需的T细胞激活状态（激活、共刺激/正常功能、耗竭、衰老）与WWH神经精神并发症之间的关联。参与女性机构间HIV研究的369名WWH（78%的HIV RNA检测不到/<20拷贝/毫升）完成了神经心理学测试以及抑郁测量（流行病学研究中心抑郁量表-CES-D）、自我报告的压力水平（感知压力量表-10）和创伤后应激（创伤后应激障碍检查表-平民版）。多参数流式细胞术评估T细胞激活状态。在调整混杂因素后，使用偏最小二乘回归来检查T细胞表型与神经精神结果的关联。在总样本和病毒抑制（VS）-WWH中，CD4 T细胞耗竭与较差的学习及注意力/工作记忆相关（P<0.05）。在总样本中，CD4 T细胞激活与较好的注意力/工作记忆相关，CD8 T细胞共刺激和衰老与较差的执行功能相关（P<0.05）。对于心理健康结果，在总样本中，CD4 T细胞激活与更多的感知压力相关，CD4 T细胞耗竭与较少的抑郁症状相关（P<0.05）。在VS-WWH中，CD4衰老与较少的感知压力相关，CD8 T细胞共刺激和衰老与较高的抑郁相关（P<0.05）。总之，结果表明外周CD4和CD8 T细胞激活状态对WWH神经精神并发症有影响。
