ObjectiveOptimism and purpose in life are associated with improved health outcomes. More information is needed on biological mechanisms, including immunosenescence. We investigated if psychological well-being is associated with healthier immunosenescence-related measures including naïve and terminally differentiated CD4+ and CD8+ T cell percentages, CD4+:CD8+, and cytomegalovirus (CMV) IgG response. MethodsParticipants were adults over age 50 from the Health and Retirement Study. Optimism was measured using the Life Orientation Test Revised. Purpose in life was assessed using the subscale from the Ryff psychological well-being measure. We examined the cross-sectional associations of optimism and purpose in life with measures of T cell subsets using linear regression and with CMV IgG using ordered logit regression, controlling for potential confounding factors. ResultsThe final analytic sample ranged from 7250 to 7870. After adjusting for sociodemographic factors, a 1-SD increment in optimism was associated with the percentage of naïve CD4+ T cells increasing by 0.6 (95%CI 0.2%, 1.0%). A 1-SD increment in purpose in life was associated with the percentage of naïve CD4+ T cells increasing by 0.9 (95%CI 0.5%, 1.3%) after adjusting for sociodemographic factors and the association was maintained after further adjustments for health conditions, depression, and health behaviors. For naïve CD8+ T cell percentages, CD4:CD8 ratios, and CMV IgG antibodies, associations were seen only in models that adjusted for age. No significant associations were seen in any models for the terminally differentiated CD4+ and CD8+ T cells. ConclusionsWe found associations of optimism and purpose in life with naïve CD4+ T cell percentages.