Age-related tyrosine-specific protein phosphorylation defect in human T lymphocytes activated through CD3, CD4, CD8 or the IL-2 receptor

Quadri, Rafael; Plastre, Olivier; Phelouzat, Marie Anne; Arbogast, Agnès; Proust, Jacques

doi:10.1016/0047-6374(96)01715-0

Cited by 43 publications

(16 citation statements)

References 26 publications

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“…A higher percentage of basal apoptotic levels in aged human PBL could indicate an impaired phagocytosis of these cells in the aging population. Several changes in lymphocytes have been observed related to aging: diminished synthesis of growth and survival factors (24)(25), impaired intracellular calcium regulation (26), different surface molecular expression (27) and defects of signal transduction (28).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant micronutrients improve intrinsic and UV-induced apoptosis of human lymphocytes particularly in elderly people

Ge²,

Zhang

et al. 2011

The Journal of nutrition, health and aging

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Section: Discussionmentioning

confidence: 99%

Antioxidant micronutrients improve intrinsic and UV-induced apoptosis of human lymphocytes particularly in elderly people

Ge²,

Zhang

et al. 2011

The Journal of nutrition, health and aging

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“…The level of tyrosine phosphorylation of p59fyn and ZAP-70 kinases is impaired in T cells from old mice activated through the TCR–CD3 complex. In human T cells, an age-related defect is observed in tyrosine-specific protein phosphorylation after activation via TCR–CD3 complexes, CD4 and IL-2 receptors [63]. In addition, a reduction in p59fyn activity was found in some elderly subjects without compensation by p56lck activity.…”

Section: Tcr and Costimulatory Signalling Changes With Ageing: A Biocmentioning

confidence: 99%

Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with ageing – a biochemical paradigm for the ageing immune system

et al. 2003

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290 APC = antigen-presenting cell; DRM = detergent-resistant microdomain; ERK = extracellular signal-regulated kinase; IFN = interferon; IL = interleukin; ITAM = immunoreceptor tyrosine-based activation motif; LAT = linker of activated T cells; mAb = monoclonal antibody; MAPK = mitogenactivated protein kinase; MHC = major histocompatibility complex; NF = nuclear factor; NFAT = nuclear factor of activated T cells; PKC = protein kinase C; pLAT, tyrosine-phosphorylated LAT; PTK = protein tyrosine kinase; RA = rheumatoid arthritis; SLE = systemic lupus erythematosus; TCR = T-cell receptor; Th cells = T helper cells; ZAP = zeta-associated protein. Arthritis Research & TherapyVol 5 No 6 Fülöp et al. IntroductionIt is widely accepted that cell-mediated immune functions (cytotoxicity, delayed-type hypersensitivity, etc.) decline with age [1,2]. These age-associated immunological changes render an individual more susceptible to infection and possibly cancer, as well as to age-associated autoimmune disorders; they may also contribute to atherosclerosis and Alzheimer's disease [3][4][5]. There is still no clear consensus as to why cell-mediated immunity declines with age. It is generally believed that age-related immune deficiency develops coincident with the gradual involution of the thymus gland and, consequently, that thymic-related (T-cell) functions are the most profoundly affected. It has recently been suggested that the alterations observed with ageing are a reflection of an accumulation of relatively inert memory T cells and a consequent AbstractIt is widely accepted that cell-mediated immune functions decline with age, rendering an individual more susceptible to infection and possibly cancer, as well as to age-associated autoimmune diseases. The exact causes of T-cell functional decline are not known. One possible cause could be the development of defects in the transduction of mitogenic signals following TCR stimulation. This T-cell hyporesponsiveness due to defects of signalling through the TCR either from healthy elderly subjects or from individuals with autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus results in an impaired ability to mount efficient immune responses and to maintain responsiveness to foreign antigens. This implies that a high proportion of autoreactive T cells might accumulate either intrathymically or in the periphery. T-cell anergy and differential TCR signalling could thus also be key players in the disruption of tolerance and the onset of autoimmune diseases. The increasing number of the elderly may lead to an increase of clinically important autoimmune diseases. We will review the signal transduction changes through the TCR-CD3 complex in T lymphocytes from healthy elderly subjects, which result in a modification of the activation of transcription factors involved in IL-2 gene expression leading to decreased IL-2 production. The putative contribution of altered T-cell signalling with ageing in the development of autoimmune diseases will be also discussed.

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“…Abnormalities in each of these processes occur in AD and can be linked to neuronal death and brain dysfunction. Some of these pathological changes are also related to aging and are additionally altered in AD by common or divergent mechanisms (Quadri et al, 1996;Poulin et al, 1996;Eckert et al, 1997a;Eckert et al, 1997b;Schindowski et al, 2000). Cell culture experiments also suggest that defects in the cellular calcium stores, ability to handle oxidative stress, and to respond to metabolic impairment, link the FADcausing PS1 mutations to the disease process (Mattson et al, 2001).…”

Section: Neuromolecular Medicinementioning

confidence: 99%

Impact of Aging: Sporadic, and Genetic Risk Factors on Vulnerability to Apoptosis in Alzheimer's Disease

Schindowski

Kratzsch

Peters

et al. 2003

NMM

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The identification of specific genetic and amyloid precursor protein [APP] mutations) and environmental factors responsible for Alzheimer's disease (AD) has revealed evidence for a shared pathway of neuronal death. Moreover, AD-specific cell defects may be observed in many other nonneuronal cells (e.g., lymphocytes). Thus, lymphocytes may serve as a cellular system in which to study risk factors of sporadic, as well as genetic AD in vivo. The aim of our present study was to clarify whether lymphocytes bearing genetic or sporadic risk factors of AD share an increased susceptibility to cell death. Additionally we examined whether a cell typespecific vulnerability pattern was present and how normal aging, the main risk factor of sporadic AD, contributes to changes in susceptibility to cell death. Here, we report that lymphocytes affected by sporadic or genetic APP and PS1 AD risk factors share an increased vulnerability to cell death and exhibit a similar cell type-specific pattern, given that enhanced vulnerability was most strongly developed in the CD4 + T-cell subtype. In this paradigm, sporadic risk factors revealed the highest impact on cell type-specific sensitivity of CD4 + T cells to apoptosis. In contrast, normal aging results in an increased susceptibility to apoptosis of both, CD4 + and CD8 + T cells.

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Age-related tyrosine-specific protein phosphorylation defect in human T lymphocytes activated through CD3, CD4, CD8 or the IL-2 receptor

Cited by 43 publications

References 26 publications

Antioxidant micronutrients improve intrinsic and UV-induced apoptosis of human lymphocytes particularly in elderly people

Antioxidant micronutrients improve intrinsic and UV-induced apoptosis of human lymphocytes particularly in elderly people

Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with ageing – a biochemical paradigm for the ageing immune system

Impact of Aging: Sporadic, and Genetic Risk Factors on Vulnerability to Apoptosis in Alzheimer's Disease

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