W133 - Lifespan Changes in CD4 T Cells and Their Implications to Aging and Neurodegenerative Diseases

Tal Katz – The Shraga Segal Department of Microbiology, Immunology and Genetics – Ben-Gurion University of the Negev; Yan Press – Department of Geriatrics – Soroka Medical Center; Boris Punchik – Clalit Health Services; Dan Vilenchik – School of Electrical and Computer Engineering – Ben-Gurion University of the Negev; alon Monsonego – The Shraga Segal Department of Microbiology, Immunology and Genetics – Ben-Gurion University of the Negev

Abstract Text: Using single-cell RNA sequencing techniques, we recently revealed lifespan changes within the CD4 T-cell compartment of mice, including a marked accumulation of cytotoxic CD4 T cells (CD4 CTLs) in late stages of aging. Here we aim to characterize the CD4 T-cell landscape across the human lifespan, especially focusing on cytotoxic subtypes and their activation properties. Furthermore, we aim to determine whether individuals with mild cognitive impairment (MCI) exhibit a more advanced stage of immunological aging.
Peripheral blood mononuclear cells (PBMCs) were isolated from human healthy male and female individuals and from elderly individuals diagnosed with MCI and were subjected to flow cytometry analysis using broad markers of CD4 T-cell subsets including cytotoxic, exhaustion and regulatory T cells (Tregs).
We revealed significant age-related changes in the CD4 T-cell landscape with a marked increase in CD4 CTL frequencies. We also observed correlations between age and frequencies of exhausted and Treg subsets. Intriguingly, elderly individuals with MCI exhibited a distinct tendency for heightened age-related alterations in the CD4 T-cell landscape. Moreover, principal component analysis of flow cytometry data revealed that the features of age-related changes in the CD4 T-cell compartment roughly predict chronological age and MCI with top features related to cytotoxic functions of CD4 T cells.
Our findings reveal substantial alterations in the CD4 T-cell landscape during human lifespan which were more abundant in individuals with MCI. We suggest that these changes gradually reduce the capacity of tissue repair and may thus linked to the biology of aging and age-related disease susceptibility.