Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging

Abstract

Clinical observations indicate that elderly people are prone to severe, often lethal infectious diseases induced by novel pathogens. Since the ability to mount primary immune responses relies on the availability of naive T cells, the circulating naive T-cell reservoir was evaluated throughout the human life span. Naive T cells were identified as CD95− T lymphocytes for their phenotypic and functional features. Indeed, the lack of CD95 marker is sufficient to identify a population of naive T cells, as defined by coincidence with previously characterized CD45RA+ CD62L+ T cells. Naive CD95− T cells, as expected, require a costimulatory signal, such as CD28, to optimally proliferate after anti-CD3 stimulation. Cytofluorimetric analysis of circulating T lymphocytes from 120 healthy subjects ranging in age from 18 to 105 years revealed that naive T cells decreased sharply with age. The younger subjects had a naive T-lymphocyte count of 825 ± 48 cells/μL, and the centenarians had a naive T-lymphocyte count of 177 ± 28 cells/μL. Surprisingly, the naive T-cell count was lower in CD8+than in CD4+ subsets at any age, and the oldest individuals were almost completely depleted of circulating naive CD8+ T cells (13 ± 4 cells/μL). Concomitantly, a progressive expansion of CD28− T cells occurs with age, which can be interpreted as a compensatory mechanism. These data provide new insights into age-related T-cell–mediated immunodeficiency and reveal some analogies of T-cell dynamics between advanced aging and human immunodeficiency virus (HIV) infection. In conclusion, the exhaustion of the naive CD8+ T-cell reservoir, which has never been reported before, suggests that this T-cell pool is a major target of the aging process and may define a parameter possibly related to the life span of humans.

The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens

“…(1). Toll-like receptor (TLR)-mediated signalling events are initiated (2) leading to increased production of cytokines and reactive oxygen species (ROS) products (3). Phagocytes initiate phagocytosis (4) resulting in the killing and removal of the pathogen.…”

“…Ageing is a biological phenomenon which occurs in all organisms. That dysfunction of the immune system occurs has been well described [1]; a decline in the normal functioning of the acquired (or adaptive) immune system [2] with a shift in the T cell population from naive T cells to memory T cells [3] leads to reduced immunization efficacy and poor acquired immune response to new pathogens. The ageing innate immune response is more complex, with increased neutrophil recruitment but decreased specific activity [1].…”

Immunity and age: living in the past?

“…Consequently, the naive T-cell pool represents an increasingly smaller proportion of the total number of available T cells with aging. Indeed, in people older than 100 years of age, naive CD8 C T cells are essentially absent [31]. Second, there is an increasing representation of T cells with a memory phenotype, driven largely by the accumulated experience of the individual with pathogenic challenge and by the homeostatic proliferation of the memory T-cell pool [21].…”

Age‐related Epstein–Barr virus‐associated B‐cell lymphoproliferative disorders in elderly White patients

“…8 The relative immunosuppression in elderly people could allow EBV-infected cells to escape control, which may favour the development of these lymphomas. 9 Blood EBV polymerase chain reaction was positive in one patient in our series, suggesting EBV replication. The diagnosis of aEBVLPD should be considered in elderly people presenting with an aggressive lymphoma, particularly those with oropharynx involvement, and EBV antigen reactivity should be systematically tested in tumour cells.…”