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

ABSTRACT

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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 enrollment in the study. RESULTS: 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. CONCLUSION: 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.