Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors.

Nagel, James; Chopra, Rajesh; Chrest, Francis J.; McCoy, Michael T.; Schneider, Edward L.; Holbrook, Nikki J.; Adler, William H.

doi:10.1172/jci113422

Cited by 250 publications

(83 citation statements)

References 44 publications

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“…Many earlier reports using different techniques to determine serum levels of cytokines indicate that the lymphocyte's response to mitogens is impaired in elderly subjects (Murasko et al, 1986;Nagel et al, 1988;Bruunsgaard et al, 2000a). In this study, we could only detect a tendency of lymphocytes from young donors to produce more IL-2.…”

Section: Discussioncontrasting

confidence: 52%

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Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsets

Schindowski

Fröhlich

Maurer

et al. 2002

Mechanisms of Ageing and Development

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The relevance of physiological immune aging is of great interest with respect to determining disorders with pathologic immune function in aging individuals. In recent years, the relevance of changes in peripheral lymphocytes in age-associated neurologic diseases has become more evident. Due to the lack of immunological studies. covering moce than one event after mitogenic activation, we envisaged a new concept in the present study, aiming to investigate several events, starting from T cell receptor (TCR) ligation up to T cell proliferation. In addition, we addressed the question whether changes are present in the subsets (CD4, CDR) with aging. Phosphorylation of tyrosine residues declines with increasing age in CD4+ cells. Fewer levels of CD69 positive cells after 4 h mitogenic activation, altered expression of cytokines (IL2, IFN-7 and TNF-a; 22 h) and lower proliferation (72 h) were detemined in aging. Moreover, it could be shown that CD8" lymphocytes react more effectively to mitogenic stirnulation with referenoe to CD69 expression and proliferation in both age groups ( < 35 and > 60 years old). These data indicate that T cell activation, rnediated by TCR engagement, is significantly impaired in aging and both subsets are affected. However, bypassing the TCR does not fully restore T cell function, indicating that there are more mechanisms involved than impaired signal transduction thwugh TCR only. The results will be discussed in relation to iiheir relevance in neurodegenerative and psychiatric disorders.

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Section: Discussioncontrasting

confidence: 52%

“…Since not only protein levels but mRNA levels of IL2 as well are de-creased in aging (Barcellini et al, 1988;Nagel et al, 1988), reduced activation of transcription factors surely is another aspect in immunosenescence.…”

Section: Discussionmentioning

confidence: 99%

Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsets

Schindowski

Fröhlich

Maurer

et al. 2002

Mechanisms of Ageing and Development

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“…The very large differences in apoptosis in the older mice would mandate an equally substantial change in lymphocytic population. It has been shown that non-functional T cells increase with age in both mouse and man, though the molecular and physiologic bases for this dysfunction is not yet clear (Song et al, 1993;Nagel et al, 1988). It will be interesting to determine in the future whether specific lymphocyte subsets, defined by surface markers, occupy a major portion of the aging peripheral immune system, and whether the same cells are deficient in their response to antigenic stimulation and in apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Less death in the dying

Polyák

Hamilton

et al. 1997

Cell Death Differ

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Diseases associated with aging are now the primary causes of death in developed countries. This is in part due to the long recognized exponential association of cancer with age and perhaps to a deterioration of the immune system with advanced age. Both prevention of tumorigenesis and immune function are critically dependent on apoptosis. In this study we examined apoptosis in mice of various age following gamma irradiation. We found a striking agedependent decrease in radiation-induced apoptosis in splenic lymphocytes but not in colorectal epithelial cells. These observations may therefore provide a clue to the decline of immune function with age.

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“…These immune functions are altered with aging [13,19,20,28]. The role of various isoforms of PKC in cell activation and proliferation is under intense investigation [9], but there are only a limited number of reports concerning PKC isoforms expression in lymphocytes with aging [23,29] The goal of the present study was to examine PKC isozyme distribution in resting and in CD3-stimulated lymphocytes of healthy elderly and young subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Several functions of T cells that either partially depend on PKC activity or are regulated by the activation of PKC exhibit abnormalities during aging [19,20]. For instance, T cells from elderly subjects stimulated through the TcR/CD3 complex show diminished production of IL2 and a decrease in IL2 receptor expression as well as reduced activation of the AP1 and NFxB transcription factors [21,22].…”

Section: Introductionmentioning

confidence: 99%

Cellular distribution of protein kinase C isozymes in CD3‐mediated stimulation of human T lymphocytes with aging

et al. 1995

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Protein kinase C (PKC) is involved in a variety of cellular responses, such as the expression and secretion of IL-2, the regulation of cytotoxic killing and cell proliferation. It is known that these immune functions are altered with aging. Here, we show that anti-CD3-triggered T cell proliferation is significantly decreased with aging and that H7, an inhibitor of PKC, impairs the anti-CD3-induced T cell proliferation in a differential manner, lymphocytes of healthy young subjects being more sensitive to the PKC inhibitor than those of elderly subjects. We examined (Western blot) the presence and the cellular distribution of PKC isozymes in T lymphocytes of healthy young and elderly subjects in the resting state and after anti-CD3 mAb stimulation using antibodies directed against PKC 6,/3, 8, e and isoforms in the cytosol and the plasma membrane fractions. These five PKC isotypes were present in human T cells of young and elderly subjects. However, their distribution between the cytosolic and membrane fractions varied according to the isozymes and the age of the subjects. In resting lymphocytes of young subjects, all the PKC isozymes were found in the cytosolic fraction, except PKC-~. In resting lymphocytes of elderly subjects PKC-~ and -e were almost equally distributed between the cytosolic and the membrane fractions, whereas PKC-, and -~ were mainly found in the membrane fraction and PKC-/3 was almost exclusively located in the cytosolic fraction. The translocation of PKC-c~, -/3, -~ and -E could be observed under anti-CD3 mAb stimulation in lymphocytes of young subjects, while in the case of elderly subjects only the PKC ]3 isoform was translocated. Our results suggest that the decreased availability of cytosolic PKC may contribute to the diminished PKC-dependent responses to CD3-triggered stimulation of human T lymphocytes with aging.

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Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors.

Cited by 250 publications

References 44 publications

Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsets

Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsets

Less death in the dying

Cellular distribution of protein kinase C isozymes in CD3‐mediated stimulation of human T lymphocytes with aging

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