Evaluating t-cell age-related immune phenotypes in the context of biological aging in health and retirement study

Abstract Cellular changes in the adaptive immune system accompanies the aging process and contributes to an age-related immune phenotype (ARIP) characterized by decrease in naïve T (TN) cells and increase in memory T (TM) cells. However, a population level marker of ARIP associated with biological aging and age-related chronic conditions has not been evaluated previously. We developed two ARIP measures based on well understood age related changes in T cell distribution: TN/ (TCM (Central Memory) + TEM (Effector Memory) + TEFF (Effector)) or TN/ TM in CD4+ and CD8+ T cells. We compared them with more commonly used ARIP measures such as CD4/CD8 ratio and CD8+ TN cells by evaluating associations with chronological age and phenotypic age using linear regression and association with multimorbidity using multinomial logistic regression. CD8+ TN and TN/TM had the strongest inverse association with chronological age (beta estimates: -3.41, -3.61; p-value< 0.0001). CD4+ TN/TM had the strongest inverse association with phenotypic age (beta estimate = -0.74; p-value < 0.0001) after adjustment for age, sex, race and CMV serostatus. CD4+ TN/TM was inversely associated with co-occurring chronic conditions (odds ratio for 2 conditions and 3 conditions vs. 0 conditions: 0.74 (95%CI: 0.63-0.86) and 0.75 (95% CI: 0.63-0.90), respectively) after adjustment for age, sex, race, CMV serostatus, smoking, and BMI. CD4+ TN/TM had a stronger association with phenotypic age and age-related morbidity compared to other ARIP measures. Future longitudinal studies can help us evaluate if CD4+ TN/TM can predict risk of aging related outcomes.