CD28 Expression in T Cell Aging and Human Longevity

Boucher, Nathalie; Dufeu‐Duchesne, Tania; Vicaut, Éric; Farge, D.; Effros, Rita B.; Schächter, François

doi:10.1016/s0531-5565(97)00132-0

Cited by 175 publications

(119 citation statements)

References 59 publications

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“…This has functional consequences. It has been suggested that the ability of centenarians´ T cells to respond by medium-term proliferation to alloactivation and mitogen-activation correlates with the percentage of CD28+ cells in their PBMC (136). These findings are reminiscent of our own, where we established that the age-associated decrease in density of expression of CD28 on CD4+ T cell clones in culture correlated with their proliferative capacity (137).…”

Section: Cd28supporting

confidence: 81%

T cells and aging (update February 1999)

Pawelec

1999

Front Biosci

113

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T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

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Section: Cd28supporting

confidence: 81%

T cells and aging (update February 1999)

Pawelec

1999

Front Biosci

113

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“…In addition, an altered TCR repertoire with age (19) during priming, changing the rate of differentiation or proportion of different memory T cell subsets. Finally, other cell-intrinsic or external factors such as inherent T cell senescence (51)(52)(53) or Tregs (23,24) could influence the initial development of T cell memory in aged mice. It is possible that more than one of these mechanisms contributes to changes in CD8 T cell memory with age.…”

Section: Discussionmentioning

confidence: 99%

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Decman

Laidlaw

DiMenna

et al. 2010

The Journal of Immunology

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Although previous studies have demonstrated delayed viral clearance and blunted effector T cell responses in aged mice during infection, memory CD8 T cells and especially secondary responses have received less attention. In this study, we show that modest differences in the number of memory CD8 T cells formed in aged versus young animals were associated with altered memory CD8 T cell differentiation. Aged immune mice had increased morbidity and mortality upon secondary viral challenge, suggesting changes in T cell immunity. Indeed, virus-specific memory CD8 T cells from aged mice showed substantially reduced proliferative expansion upon secondary infection using multiple challenge models. In addition, this defect in recall capacity of aged memory CD8 T cells was cell-intrinsic and persisted upon adoptive transfer into young mice. Thus, the poor proliferative potential of memory T cells and altered memory CD8 T cell differentiation could underlie age-related defects in antiviral immunity.

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“…10,11 The majority of studies on aging and immune function have focused on adaptive T cell function, with several reports showing that aging impairs T cell IL-2, IFN-γ production, and Th1 immunity, [12][13][14] one of the critical immune defenses to infection from intracellular pathogens such as viruses. Aging also impairs T-cell CD28 signaling 15 and immune synapse formation. 16 Furthermore, aging reduces T cell thymic output, leading to reduced numbers of naïve T cells, cells that are essential for eradicating infections from new pathogens.…”

Section: Current Paradigm Concerning How Aging Impacts Immune Functionmentioning

confidence: 99%

Aging, imbalanced inflammation and viral infection

Goldstein¹

2010

Virulence

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CD28 Expression in T Cell Aging and Human Longevity

Cited by 175 publications

References 59 publications

T cells and aging (update February 1999)

T cells and aging (update February 1999)

Cell-Intrinsic Defects in the Proliferative Response of Antiviral Memory CD8 T Cells in Aged Mice upon Secondary Infection

Aging, imbalanced inflammation and viral infection

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