Inhibitory receptor signatures on gamma delta T cells predict ART-suppressed HIV infection, are synergistically altered by HIV and aging, and co-vary with inflammatory plasma analytes

• Published in: The Journal of immunology (1950) Vol. 200; no. Supplement_1; pp. 182 - 182.15
• Main Authors: Snyder-Cappione, Jennifer E, Belkina, Anna C, Starchenko, Alina, Drake, Katherine, Proctor, Elizabeth, Lauffenburger, Douglas A, Browning, Jeffrey L, Olson, Alex, Lin, Nina H
• Format: Journal Article
• Language: English
• Published: 01.05.2018
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.182.15

Virologically suppressed HIV+ individuals have an increased risk and earlier onset of age-associated diseases such as cardiovascular atherosclerosis, cancer, and osteoporosis, referred to as HIV-Associated Non-AIDS conditions (HANAs). Whether HIV drives HANAs via same mechanisms as normal aging or other processes is unclear. We analyzed PBMC from 45 ART-suppressed HIV+ subjects (20 ≤35yo ‘younger’, 25 ≥50yo ‘older’) and 39 uninfected controls (20 younger, 19 older) with a 16-color flow cytometry panel that measures the inhibitory receptors (IRs) PD-1, TIGIT, CD160, TIM-3, and LAG-3 on CD4+ T cells, CD8+ T cells, NK cells, iNKT cells, and gd T cells. Bioinformatic (CITRUS) analysis revealed that gd T cell IR expression exclusively differentiated HIV+ subjects from controls. Also, a synergistic effect of HIV and aging on TIGIT+ and ≥ 2 IR gd T cell percentages was found. gd T cell functional profiling revealed a positive association between TIGIT expression and spontaneous release of granzymes A and B from HIV+ subjects but not controls. Using supervised multivariate modeling (Partial Least Squares discriminant analysis, PLS) of gd T IR signatures, gd T cell cytokine secretion, and inflammatory plasma analytes, all four subject groups (HIV+ and uninfected, ≤35 and ≥50yo) were effectively distinguished. Also, a statistically significant covariance between gd T cell IR signatures and levels of inflammatory plasma analytes, including IL-6, IL-1b and fibrinogen was found. Our data implicate gd T cells as a key inflammatory driver in ART-suppressed HIV infection and our PLS results suggest a divergence of ART-suppressed HIV inflammation and healthy aging processes, revealing differential "inflammaging" with and without HIV infection.