T cell subset-specific susceptibility to aging

Abstract

With increasing age, the competence of the immune system to fight infections and tumors declines. Age-dependent changes have been mostly described for human CD8 T cells, raising the question of whether the response patterns for CD4 T cells are different. Gene expression arrays of memory CD4 T cells yielded a similar age-induced fingerprint as has been described for CD8 T cells. In crosssectional studies, the phenotypic changes were not qualitatively different for CD4 and CD8 T cells, but occurred much more frequently in CD8 T cells. Homeostatic stability partially explained this lesser age sensitivity of CD4 T cells. With aging, naïve and central memory CD8 T cells were lost at the expense of phenotypically distinct CD8 effector T cells, while effector CD4 T cells did not accumulate. However, phenotypic shifts on central memory T cells were also more pronounced in CD8 T cells. This distinct stability in cell surface marker expression can be reproduced in vitro. The data show that CD8 T cells are age sensitive by at least two partially independent mechanisms: fragile homeostatic control and gene expression instability in a large set of regulatory cell surface molecules.

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

“…CD45RA + memory cells (T EMRA ) have lost the expression of CD28, CD27, and CCR7 and exhibit a low proliferative capacity, a high susceptibility to apoptosis, short telomeres, and high levels of perforin and Fas ligand; thus, T EMRA cells represent the most differentiated type of memory cell (Hamann et al 1997;Geginat et al 2003;Fritsch et al 2005). This age-associated shift has been reported to occur more intensely in the CD8 + cell compartment than the CD4 + T cell compartment (Czesnikiewicz-Guzik et al 2008). In fact, in our nontrained elderly, T EMRA cells accounted for ∼15 % of the CD8 + T cells and only ∼5 % of the CD4 + T cells.…”

Relationship between functional ability in older people, immune system status, and intensity of response to CMV

“…The two subsets undergo the same principal phenotypic shifts, but the rate at which they occur or accumulate with age was different. CD4+ T cells were more resistant to phenotypic and functional changes with aging than CD8+ T cells (Czesnikiewicz-Guzik et al 2008).…”

Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age

“…Once cells have emigrated into the periphery, stochastic homeostatic turnover should occur at an average rate of ∼0.001 per cell per day as suggested by labeling studies of naive T cells (40). The total T-cell population size for a young human adult is ∼3 × 10 11 ; the percentage of this population that is naive decreases with age from ∼50% to ∼30% for CD4 cells (19). Further, thymic involution, which occurs at a rate of at least 3% per year until age 40, and 1% thereafter (14,41), should lead to a corresponding decline in the rate of thymic emigrants.…”

“…The conventional view is that the loss of diversity arises as a consequence of (i) involution of the thymus and the related decline in the production of new naive T cells (14)(15)(16)(17); (ii) stochastic extinction resulting from drift in the number of cells in different lineages during homeostatic turnover (2,18) or, equivalently, from the perspective of the naive population, conversion of naive cells into memory cells (18); and (iii) a decline in the total number of naive T cells with age (18,19). Recent work showed elegantly that the thymus, though critical to sustaining the naive T-cell population size in adult mice, plays a minor role in sustaining this population in adult humans (20).…”