Evaluation of T-cell aging-related immune phenotypes in the context of biological aging and multimorbidity in the Health and Retirement Study

AbstractBackgroundCellular changes in adaptive immune system accompany the process of aging and contribute to an aging-related immune phenotype (ARIP) characterized by decrease in naïve T-cells (TN) and increase in memory T-cells (TM). A population-representative marker of ARIP and its associations with biological aging and age-related chronic conditions have not been studied previously.MethodsWe developed two ARIP indicators based on well understood age-related changes in T cell distribution: TN/(TCM(Central Memory) + TEM(Effector Memory) + TEFF(Effector)) (referred as TN/TM) in CD4 + and CD8 + T-cells. We compared them with existing ARIP measures including CD4/CD8 ratio and CD8 + TN cells by evaluating associations with chronological age and the Klemera Doubal measure of biological age (measured in years) using linear regression, multimorbidity using multinomial logistic regression and two-year mortality using logistic regression.ResultsCD8 + TNand CD8 + TN/TMhad the strongest inverse association with chronological age (beta estimates: -3.41 and -3.61 respectively;p-value < 0.0001) after adjustment for sex, race/ethnicity and CMV status. CD4 + TN/TMand CD4 + TN had the strongest inverse association with biological age (β = -0.23;p = 0.003 and β = -0.24;p = 0.004 respectively) after adjustment for age, sex, race/ethnicity and CMV serostatus. CD4/CD8 ratio was not associated with chronological age or biological age. CD4 + TN/TMand CD4 + TNwas inversely associated with multimorbidity. For CD4 + TN/TM, people with 2 chronic conditions had an odds ratio of for 0.74 (95%CI: 0.63–0.86p = 0.0003) compared to those without any chronic conditions while those with 3 chronic conditions had an odds ratio of 0.75 (95% CI: 0.63–0.90;p = 0.003) after adjustment for age, sex, race/ethnicity, CMV serostatus, smoking, and BMI. The results for the CD4 + TNsubset were very similar to the associations seen with the CD4 + TN/TM. CD4 + TN/TMand CD4 + TNwere both associated with two-year mortality (OR = 0.80 (95% CI: 0.67–0.95;p = 0.01) and 0.81 (0.70–0.94;p = 0.01), respectively).ConclusionCD4 + TN/TMand CD4 + TNhad a stronger association with biological age, age-related morbidity and mortality compared to other ARIP measures. Future longitudinal studies are needed to evaluate the utility of the CD4 + subsets in predicting the risk of aging-related outcomes.