Category: Immunity & infection
Our previous work implicates γδ T cells as an inflammatory driver in ART-suppressed HIV infection and suggests that this unique T cell population serves distinct roles in the ‘inflamm-aging’ that occurs with age with and without aviremic HIV. We sought to determine the precise γδ T cell subsets that are driving inflammation with age +/- HIV infection. We performed in depth immunophenotyping of circulating γδ T cells via multi-color flow cytometry and analysis of plasma markers of inflammation, coagulation, and intestinal permeability from subjects of our HIV and Aging cohort, which includes ART-suppressed HIV+ individuals and matched uninfected controls stratified by age into younger (≤35yo) and older (≥50yo) groups. We found discrete differences in the combinational expression the inhibitory receptors (IRs) TIGIT, PD-1, and CD160 between the Vδ1+ and the Vδ2+ γδ T cell subsets with HIV infection and healthy aging. Also, we found that the specific IR signatures of Vδ1+ and Vδ2+ γδ T cells correlated with plasma inflammatory markers; however, different connections between the plasma analytes were found for each of the two γδ T cell subsets. Taken together, these data indicate that Vδ1+ and Vδ2+ γδ T cells exist in distinct states and possess divergent roles in the ‘inflamm-aging’ found in aviremic HIV+ infection and with normal aging. Further investigation into the anatomical locations, ex vivo functions, and additional surface markers that define γδ T cell subsets may reveal novel therapeutic targets to abrogate the aberrant inflammation found with HIV infection, aging, and other inflammatory conditions.
Anna Belkina– Boston Universtiy School of Medicine
Riley Pihl– Boston University School of Medicine
Alex Olson– Boston Medical Center
Nina Lin– Boston Medical Center
Jennifer Snyder-Cappione– Assistant Professor, Boston University School of Medicine