Reference values for CD4+ and CD8+ T lymphocytes with naïve or memory phenotype and their association with mortality in the elderly

Well-established reference values which take into account the influence of age on immune cell phenotype, and the impact of naïve or memory T cells on mortality have not been well defined in the elderly. The aim of this study was to evaluate the reference values for the peripheral number of total and naïve or memory CD4 and CD8 T cells in a healthy population in Italy, and to analyze whether the immune phenotype was associated with an increased risk of death among older adults. The number of total or naïve and memory CD4+ or CD8+ T cells was evaluated in the peripheral blood of 288 healthy people ranging in age from 20 to 107 years. Furthermore, to correlate peripheral immune phenotype with mortality rate after a 3-years follow-up, a retrospective analysis was performed on the results from those individuals aged >65 years at the time of the enrolment in the study. The absolute number of total and naïve T cells was progressively reduced with increasing age in both the CD4+ and CD8+ T cell populations. The decrease was particularly evident for cells with naïve phenotype, since CD4-naïve and CD8-naïve T cells respectively showed a 4- and a 2- to 3-fold reduction in 70- to >90-year-old subjects in comparison with young adults. The number of CD4 memory T cells significantly increased with age. No significant age-related change was observed in the number of CD8+ memory T cells. Of the 194 subjects included in the study of association of immune phenotype with mortality, 121 were alive and 73 deceased during the 3-year follow-up. The impact of immune parameters on survival demonstrated that only the absolute number of CD8 memory T cells, after adjustment for age, correlated with increased mortality (OR 1.007, 95% CI 1.002-1.012, p = 0.01). The correlation was significant in female but not in male subjects. We provide reference values for total and naïve or memory CD4 and CD8 T cell populations, and demonstrate that the absolute number of CD8 memory T cells, after adjustment for age, correlates with increased mortality.