W122 - Developing Trajectories of Immunosenescence in Diverse Adults

Immunosenescence (ISC) is the natural aging of the immune system, involving gradual changes in immune-cell proportions and functions. Genetic variation, sexual-dimorphism and previous viral infections may influence it. Thus far, limited large-scale studies are available, mostly involving European descends, although clear multi-modal ISC-trajectories remain unknown. To characterize ISC phenotypic/functional changes in a large-scale manner, we used PBMC samples (n=257, age: 18-84 years) part of two Columbia aging-cohorts.

Multiparametric-cytometry profiles, single-cell-RNA-sequencing, bulk-PBMC RNA-sequencing and T-cell proliferation were captured. First, we used standard FlowJo bi-dimensional gating to analyze cell-proportions and MFI of main innate and adaptive immune-cells, plus other markers: CD11c, CD57, PD-1/PD-1L & KLRG-1. Second, we processed .fcs files to create a multidimensional data matrix analyzed using PhenoGraph algorithm to empirically cluster PBMCs into 20 discrete cell-subtypes.

Preliminary analyses of a cohort representative (n=60), confirms previous findings: decrease in naïve CD8 T-cells (p=0.000054), increase of CD8 TEMRA T-cells (p=0.0027), and decrease of CD20⁺B-cells (p=0.0028), while CD11c⁺CD20⁺ B-cells increased with advancing age. No meaningful age-associated changes were noted in IgD⁺naïve, nor IgD^-/+CD27⁺memory B-cells. We further found a population of CD56⁺CD8⁺NKT-cells increasing with age (p=0.0019). Next, our clustering analysis uncovered an unexpected subset of CD56⁺PD-L1⁺NK-cells increasing with age (p=0.000096).

We report several aging-related cell populations including well-known ones. ISC signatures included NKT-cells and CD11c⁺B-cells. Surprisingly, we identified an intriguing senescent PD-1L⁺NK population, perhaps contributing to higher cancer incidence in elderly. Results from n=257 will be presented, enabling ISC-trajectories assessment amongst African-American, Latin-x, and non-Hispanic Whites in an ongoing effort to establish personalized ISC-trajectories.