Non-regulatory CD8⁺CD45RO⁺CD25⁺ T-lymphocytes may compensate for the loss of antigen-inexperienced CD8⁺CD45RA⁺ T-cells in old age

Abstract

The age-related decline in immune system functions is responsible for the increased prevalence of infectious diseases and the low efficacy of vaccination in elderly individuals. In particular, the number of peripheral naive T-cells declines throughout life and they exhibit severe functional defects at advanced age. However, we have recently identified a non-regulatory CD8+CD45RO+ CD25+ T-cell subset that occurs in a subgroup of healthy elderly individuals, who still exhibit an intact humoral immune response following influenza vaccination. Here, we demonstrate that CD8+CD45RO+CD25+ T-cells share phenotypic and functional characteristics with naive CD8+CD45RA+CD28+ T-cells from young individuals, despite their expression of CD45RO. CD8+CD45RO+ CD25+ T-cells also have long telomeres and upon antigenic challenge, they efficiently expand in vitro and differentiate into functional effector cells. The expanded population also maintains a diverse T-cell receptor repertoire. In conclusion, CD8+CD45RO+CD25+ T-cells from elderly individuals compensate for the loss of functional naive T-cells and may therefore be used as a marker of immunological competence in old age.

CD8 T Cells in Old Mice Contribute to the Innate Immune Response toMycobacterium tuberculosisvia Interleukin-12p70-Dependent and Antigen-Independent Production of Gamma Interferon

“…In addition to the immune defects in the T-cell compartment, significant deficiencies in B cells (27), NK cells (21,22), macrophages (15,20), and dendritic cells (19,28) have been reported. Despite the abundant evidence that the immune system of the aged is significantly altered, there is mounting data suggesting that some components of the immune system, particularly CD8 T cells, remain functionally intact or are enhanced in old age (11,26,34). The characterization of immune responses in the elderly, specifically to pathogens, may lead to more effective vaccination and therapeutic strategies in this highly vulnerable and expanding population.…”

Can the Immune System Still Be Efficient in the Elderly? An Immunological and Immunoendocrine Therapeutic Perspective

“…Nevertheless, the accumulation of CD28-T cells is also reported from immunodeficiency disorders like HIV and is one of the most consistent biological indicators of aging in the human immune system. Representing the gradual shrinkage of the naïve T cell pool (naïve T cells per definition express CD28), those CD28-T cells are long-lived lymphocytes, with unclear susceptibility to apoptosis-inducing stimuli [59,60] , and have limited proliferative and functional capacity [10,52] as well as senescence-like shortened telomeres [12,61] . Since the loss of CD28-in CD4+ T cells is accompanied by a defect in CD154 (CD40L) expression, their capacity to provide help for B cell proliferation and antibody production is reduced.…”

“…However, phenotypically naïve T cells from the elderly are not only reduced in numbers due to diminished thymic output and restricted immunological space, but also show shortened telomeres and clonal expansion ( fig. 2 ) [34,61,67] , as well as an overall compromised responsiveness to neoantigens [53,68,69] . A possible explanation for such reduced functionality of naïve T cells in the elderly could be that a significant portion of them might have undergone homeostatic proliferation [70][71][72][73] and/or have been exposed to cross-reactive autoantigen [74][75][76] .…”

“…A possible explanation for such reduced functionality of naïve T cells in the elderly could be that a significant portion of them might have undergone homeostatic proliferation [70][71][72][73] and/or have been exposed to cross-reactive autoantigen [74][75][76] . However, recently published data suggest that in elderly humans other T cell subsets can take over certain naïve functions, hence compensating for age-related loss of naïve T cells [61,77] .…”

“…Altogether, these age-related impairments in T and B cell responses result in dramatically reduced ability to clear pathogens, comprised response to vaccinations, diminished immunological memory and high risk of infections and autoimmune diseases in the elderly. Impact of aging on T cell subsets as exemplified for phenotypically naïve human CD8+ CD45RA+ CD28+ T cells (modified from Pfister et al [34] and Herndler-Brandstetter et al [61] ). a Clonal composition of purified cells from healthy young and elderly humans.…”