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 enrolment 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.

Immune dysregulation underlies a subset of patients with chronic idiopathic pruritus

“…Additionally, their CD8lymphopenia confirms the loss of Th1 responses, further supporting age-dependent Th2 polarization as a potential contributor to the development of chronic itch. Strikingly, comparison to age-matched control populations indicates that our CIP patients suffer from immunologic imbalances in excess of similarly-aged peers [4, 5]. Three of our patients’ CD8 + T cell counts were significantly reduced in comparison to control subjects of corresponding age; for example, the CD8 + T cell count of 67/mm 3 in Case 3 was nearly two standard deviations below the mean reported by Provinciali et al [4].…”

The Effect of Aging on Pulmonary Function

“…This in turn reduces the magnitude of the adaptive immune response that can be mounted against a new infection. [45][46][47] Similarly, with age, B cells have a reduced antibody-secreting capacity, 48 subsequently resulting in a less-effective antigen-specific response. The reduced effectiveness of both innate and adaptive immune responses accounts for the vulnerability of elderly patients to respiratory pathogens and injury.…”

PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit

“…Most notably, older individuals tend to have a greater abundance of late-stage differentiated memory T cells and fewer naïve T cells (Bisset et al, 2004; Provinciali et al, 2009; Xu et al, 1993). Psychosocial stress is a key modulator of activity of the neuroendocrine system, and in particular, the hypothalamic–pituitary–adrenal axis and the sympathetic–adrenal–medullary systems, which are known to affect the immune system and contribute to immune aging (Effros, 2011; Pace and Heim, 2011).…”