Peripheral CD8⁺ T cell subsets and physical frailty in community-dwelling older Thai adults: the role of age and multimorbidity

Abstract

Background: Age-related immune decline is basically recognized as a key contributor to frailty. However, associations between immune markers, including T cell subsets, and frailty remain inconclusive and data from Southeast Asia are limited. This study investigated CD8⁺ T cell phenotypes and their associations with frailty among community-dwelling older Thai adults, aiming to identify blood-based biomarkers indicative of immune decline related to frailty. Methods: In this cross-sectional study, 189 adults aged ≥ 60 years were classified as robust, pre-frail, or frail using Fried’s criteria. CD8⁺ T cell subsets—naïve (TN), central memory, effector memory, and terminally differentiated effector memory RA⁺ (TEMRA)—and expression of CD28 and PD-1 were analyzed by flow cytometry. Multivariable ordinal logistic regression was performed to identify independent predictors of pre-frailty and frailty, with sex-stratified analyses. Results: Reduced TN and increased TEMRA CD8⁺ T cells were clearly shown in our study population of older Thai adults. Frail participants exhibited significantly lower TN and higher TEMRA proportions than robust individuals. TN depletion predominated in frail females, whereas TEMRA expansion was more pronounced in frail males. In addition, CD28⁻ and PD-1⁺ phenotypes within the TN gate were increased in frail adults. In the adjusted analyses, the percentage of CD28⁻ TN (OR = 1.649, p = 0.003), age (OR = 1.222, p < 0.001), and number of comorbidities (OR = 1.334, p = 0.003) independently predicted frailty severity. Sex-stratified analyses showed that age and comorbidity burden were consistently associated with frailty, while the association with immune markers was attenuated. Conclusion: Alterations in CD8⁺ T cell phenotypes, particularly naïve T cell depletion and increased CD28⁻ cells within the TN subset, were associated with frailty among community-dwelling older Thai adults. Female and male participants exhibited different CD8⁺ T cell subset distributions; however, these sex-specific patterns were not independently associated with frailty. These findings suggest that the immune alterations observed in frailty may partly reflect age-related immune changes and underlying health conditions, while chronological age and multimorbidity remain important factors associated with frailty in this population. Trial registration number: Not applicable.