T-cell activation state differentially contributes to neuropsychiatric complications in women with HIV

Dionna W Williams; Bianca R Flores; Yanxun Xu; Yuezhe Wang; Danyang Yu; Brandilyn A Peters; Adebola Adedimeji; Tracey E Wilson; Daniel Merenstein; Phyllis C Tien; Mardge H Cohen; Kathleen M Weber; Adaora A Adimora; Igho Ofotokun; Margaret Fischl; Janet Turan; Bülent Turan; Geoffroy Laumet; Alan L Landay; Raha M Dastgheyb; Stephen J Gange; Sheri D Weiser; Leah H Rubin

doi:10.1016/j.bbih.2022.100498

T-cell activation state differentially contributes to neuropsychiatric complications in women with HIV

Brain Behav Immun Health. 2022 Aug 29:25:100498. doi: 10.1016/j.bbih.2022.100498. eCollection 2022 Nov.

Authors

Dionna W Williams^{1

2}, Bianca R Flores¹, Yanxun Xu^{3

4}, Yuezhe Wang³, Danyang Yu³, Brandilyn A Peters⁵, Adebola Adedimeji⁵, Tracey E Wilson⁶, Daniel Merenstein⁷, Phyllis C Tien⁸, Mardge H Cohen⁹, Kathleen M Weber¹⁰, Adaora A Adimora¹¹, Igho Ofotokun¹², Margaret Fischl¹³, Janet Turan¹⁴, Bülent Turan¹⁵, Geoffroy Laumet¹⁶, Alan L Landay¹⁷, Raha M Dastgheyb¹⁸, Stephen J Gange¹⁹, Sheri D Weiser^{8

20}, Leah H Rubin^{1

19

18

21}

Affiliations

¹ Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA.
⁴ Division of Biostatistics and Bioinformatics at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
⁶ Department of Community Health Sciences, State University of New York Downstate Health Science University, School of Public Health, Brooklyn, NY, USA.
⁷ Department of Family Medicine, Georgetown University Medical Center, Washington, DC, USA.
⁸ Department of Medicine, UCSF and Medical Service, Department of Veteran Affairs Medical Center, San Francisco, CA, USA.
⁹ Department of Medicine, Stroger Hospital, Chicago, IL, USA.
¹⁰ Cook County Health/Hektoen Institute of Medicine, Chicago, IL, USA.
¹¹ Division of Infectious Disease, University of North Carolina at Chapel Hill, NC, USA.
¹² Department of Medicine, Emory University and Grady Healthcare System, Atlanta, Georgia Mailman School of Public Health, Columbia University, NY, NY, USA.
¹³ Department of Medicine, University of Miami Health System, Miami, FL, USA.
¹⁴ Departments of Health Policy and Organization, School of Public Health, University of Alabama at Birmingham, USA.
¹⁵ Department of Psychology, Koc University, Istanbul, Turkey.
¹⁶ Department of Physiology, Michigan State University, East Lansing, MI, USA.
¹⁷ Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
¹⁸ Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁹ Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
²⁰ Division of HIV, ID and Global Medicine, Department of Medicine, UCSF, San Francisco, CA, USA.
²¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

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 (P'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 (P'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 (P'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 (P's < 0.05). Together, results suggest the contribution of peripheral CD4⁺ and CD8⁺ T-cell activation status to neuropsychiatric complications in WWH.

Keywords: Cognition; HIV; Mental health; T-cell function; Women.

Abstract

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