Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging

Frontiers in Immunology

Katherine A. Drake¹  Alina Starchenko²  Elizabeth A. Proctor²  Douglas A. Lauffenburger²  Nina Lin³  Alex Olson³  Jennifer E. Snyder-Cappione⁴  Anna C. Belkina⁵  Riley M. F. Pihl⁶ 

[1] Cytobank, Inc., Santa Clara, CA, United States;Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States;Department of Medicine, Boston University School of Medicine, Boston, MA, United States;Department of Microbiology, Boston University School of Medicine, Boston, MA, United States;Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, United States;Flow Cytometry Core Facility, Boston University School of Medicine, Boston, MA, United States;

关键词: γδ T cell;    TIGIT;    HIV;    aging;    inflammation;    citrus;   

DOI  :  10.3389/fimmu.2018.02783

来源: DOAJ

【 摘 要 】

Even with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic HIV infection are not yet elucidated. Also, whether ART-suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear. In this study we measured combinational expression of five inhibitory receptors (IRs) on seven immune cell subsets and 16 plasma markers from peripheral blood mononuclear cells (PBMC) and plasma samples, respectively, from a HIV and Aging cohort comprised of ART-suppressed HIV-infected and uninfected controls stratified by age (≤35 or ≥50 years old). For data analysis, multiple multivariate computational algorithms [cluster identification, characterization, and regression (CITRUS), partial least squares regression (PLSR), and partial least squares-discriminant analysis (PLS-DA)] were used to determine if immune parameter disparities can distinguish the subject groups and to investigate if there is a cross-impact of aviremic HIV and age on immune signatures. IR expression on gamma delta (γδ) T cells exclusively separated HIV+ subjects from controls in CITRUS analyses and secretion of inflammatory cytokines and cytotoxic mediators from γδ T cells tracked with TIGIT expression among HIV+ subjects. Also, plasma markers predicted the percentages of TIGIT+ γδ T cells in subjects with and without HIV in PSLR models, and a PLS-DA model of γδ T cell IR signatures and plasma markers significantly stratified all four of the subject groups (uninfected younger, uninfected older, HIV+ younger, and HIV+ older). These data implicate γδ T cells as an inflammatory driver in ART-suppressed HIV infection and provide evidence of distinct “inflamm-aging” processes with and without ART-suppressed HIV infection.

【 授权许可】

Unknown