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

• Published in: Immunity & ageing Vol. 19; no. 1; pp. 33 - 12
• Main Authors: Ramasubramanian, Ramya, Meier, Helen C S, Vivek, Sithara, Klopack, Eric, Crimmins, Eileen M, Faul, Jessica, Nikolich-Žugich, Janko, Thyagarajan, Bharat
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20-07-2022; BioMed Central; BMC
• Subjects: Adaptive immunity; Age; Aging; Biological aging; Biomarkers; Cancer; Cardiovascular disease; CD4 antigen; CD8 antigen; Chronic illnesses; Comorbidity; Comparative analysis; Cytokines; Cytomegalovirus; Diabetes; Ethnicity; Flow cytometry; Genetic aspects; Health and Retirement Study; Heart; Hispanic people; Immune aging; Immune system; Immunological memory; Lung diseases; Lymphocytes; Lymphocytes T; Memory cells; Minority & ethnic groups; Morbidity; Mortality; Multimorbidity; Phenotypes; Population; Serology; Sex; T cells; Immune aging; Adaptive immunity; Health and Retirement Study; Biological aging; Multimorbidity
• ISSN: 1742-4933; 1742-4933
• DOI: 10.1186/s12979-022-00290-z

Cellular 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 (T
) and increase in memory T-cells (T
). A population-representative marker of ARIP and its associations with biological aging and age-related chronic conditions have not been studied previously.
We developed two ARIP indicators based on well understood age-related changes in T cell distribution: T
/(T
(Central Memory) + T
(Effector Memory) + T
(Effector)) (referred as T
/T
) 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.
CD8 + T
and CD8 + T
/T
had 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 + T
/T
and CD4 + T
 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 + T
/T
and CD4 + T
was inversely associated with multimorbidity. For CD4 + T
/T
, people with 2 chronic conditions had an odds ratio of for 0.74 (95%CI: 0.63-0.86 p = 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 + T
subset were very similar to the associations seen with the CD4 + T
/T
. CD4 + T
/T
and CD4 + T
were 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).
CD4 + T
/T
and CD4 + T
had 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.