Age-related differences in phenotype and function of CD4+ T cells are due to a phenotypic shift from naive to memory effector CD4+ T cells

Abstract

Based on the combined expression of CD27 and CD28, a putative model of T cell differentiation has been previously proposed. We used CD27 and CD28 expression in order to comparatively study the size, cytokine production capacity and proliferative response of CD4+ T cell sub-populations from healthy young and elderly volunteers. Elderly persons had a lower percentage of CD27+CD28+ but a higher percentage of CD27-CD28+ and CD27-CD28-CD4+ T cells than the young persons. CD27-CD28-CD4+ T cells were present, although at relatively low numbers, in the vast majority of the healthy elderly donors but were only sporadically detected in young persons. Each CD4+ T cell sub-population exhibited a distinct phenotype and cytokine production profile, which were not affected by age. When purified CD27+CD28+ were stimulated by staphylococcal enterotoxin B, they proliferated to a greater extent than CD27-CD28+ and CD27-CD28-CD4+ T cells. However, we did not observe age-related differences in proliferative response of each sub-population. We concluded that although the size of the different sub-populations differed between the young and the old group, the functional characteristics of each sub-population were the same in both age groups. This suggests that on a per cell basis there is no functional impairment of CD4 memory T cells in elderly persons. Consequently, potential differences in the function of the total CD4+ T cell population are most likely due to different composition of repertoire.

Competitive SWIFT cluster templates enhance detection of aging changes

“…Similarly, a decrease in gamma‐delta T cells has been reported previously 24, 25. Although CD27 expression was variable in the clusters detected by SWIFT, clusters 913, 1,328, and 908 were memory CD4 T cells that expressed low levels of CD27 and were over‐represented in the elderly, consistent with previous studies 26, 27, 28. Thus the competitive template assignment in SWIFT identified many potentially different clusters between young and elderly.…”

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…39 Kovaiou at al. 40 studied CD4 subsets in healthy young and elderly volunteers finding increased CD27CCD28C T-cells (na€ ıve and early-differentiated cells) in younger people, while elderly presented more frequently CD27-CD28-T-cells (fully differentiated cells) demonstrating that the aging process was linked to a shift of CD4 T-cells from na€ ıve and early-differentiated to late differentiated subset. To better differentiate these phenotypes, the authors measured the presence of cell-surface markers, in particular CD45RA, receptors involved in lymphocyte homing [CCR7] and intercellular adhesion and co-stimulation [CD11a] associated with the different cellular subset ability to produce perforin.…”

“…Finally the analysis of telomere length revealed a significantly shorter length in CD27-CD28-CD4C cells when compared with CD27CCD28CCD4C T-cells. 40 While CD4C na€ ıve T-cells decrease with age, memory CD4C T-cells expand thanks to the continuous antigen presentation and to homeostatic proliferation. [40][41][42] T lymphocytes with specificity for a particular pathogen can persist in the host for many years after the pathogen has been eliminated.…”

“…40 While CD4C na€ ıve T-cells decrease with age, memory CD4C T-cells expand thanks to the continuous antigen presentation and to homeostatic proliferation. [40][41][42] T lymphocytes with specificity for a particular pathogen can persist in the host for many years after the pathogen has been eliminated. 43 CD8C T lymphocytes can persist without re-exposure to antigen, either from exogenous sources or from antigen depots that might be maintained after the resolution of primary infection.…”

“…43 HIV-infected patients have several similarities to older people as increased memory cells proliferation compared with na€ ıve cells. 16,40,45,46 In particular HIV-1 infection is related to: a) reduction of naive CD4C and CD8C T-cells and an increased frequency of memory CD8C T-cells; b) alterations in expression of CD27 and CD28 in chronic HIV-1 infection (as with aging) regardless of age; c) significantly shorter telomere length of CD28-CD8C T-cells and d) shift to a replicative senescent phenotype of CD28-CD8C T-cells. The sum of these changes greatly limits the capability of the CD8C T-cell compartment to perform an appropriate response against HIV-1 and other antigens.…”