T Lymphocyte Subpopulations and Activation Markers Correlate with Severity of Alzheimer's Disease

Shalit, F.; Sredni, Benjamin; Brodie, Chaya; Kott, Edna; Huberman, M.

doi:10.1006/clin.1995.1078

Cited by 89 publications

(73 citation statements)

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“…The findings support the hypothesis that changes in certain peripheral immunophenotypes occur in MCI patients. The decrease in lymphocytes in MCI subjects is consistent with reports of a decrease in the proliferative ability of lymphocytes from AD patients compared to controls (Shalit et al, 1995). Furthermore, our results of increased granulocytes in MCI subjects are in agreement with the findings of Licastro et al (1994)who found granulocyte activity to be increased in AD but not in Parkinson's disease patients, suggesting an inflammatory state specific to AD.…”

Section: Discussionsupporting

confidence: 92%

“…1999) and CD8+ lymphocytes have been shown to be decreased in AD relative to healthy aged-matched controls (Pirttila et al, 1992). Furthermore, Shalit et al (1995)have demonstrated that in moderately severe, but not mild AD patients, there was a significant decrease in lymphocyte proliferation compared to controls. A decrease in proliferation in peripheral blood mononuclear cells (PBMCs) of AD patients has also been found (Lombardi et al, 1999).…”

Section: Introductionmentioning

confidence: 95%

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Immunophenotypes in the circulation of patients with mild cognitive impairment

Magaki

Yellon

Mueller

et al. 2008

Journal of Psychiatric Research

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Alterations in the peripheral immune system are associated with dementia and the neuropathology of Alzheimer's disease, but have yet to be studied early in the disease process. To test the hypothesis that the balance of immune cell phenotypes is disrupted in the early progression of memory deterioration, patients with mild cognitive impairment (MCI) and healthy elderly controls were examined for the distribution of subpopulations of leukocytes (lymphocytes, granulocytes, and monocytes) and lymphocyte subtypes (helper/inducer and suppressor/cytotoxic T lymphocytes and B lymphocytes) in blood. MCI subjects had a significantly higher percentage of total lymphocytes and a lower percentage of granulocytes compared to elderly controls. Furthermore, the expression of cell surface amyloid precursor protein (APP) and intracellular amyloid-β peptide (Aβ) in lymphocytes and monocytes were determined. We found lymphocyte APP expression to be significantly increased in MCI subjects compared to controls. Our data indicate that changes in immunological parameters may be detected early in MCI, and an alteration of the immune response may precede clinical AD.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 95%

Immunophenotypes in the circulation of patients with mild cognitive impairment

Magaki

Yellon

Mueller

et al. 2008

Journal of Psychiatric Research

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“…Further, CD95-induced apoptosis is not altered in AD, indicating that mechanisms are evident here that do not contribute to accelerated aging in AD. Moreover, different but not typical age-related expression of activation markers and members of the Bcl-2 family has been reported in dementia of the Alzheimer's type in brain tissue [11,19,30] and as well in AD lymphocytes [33,44]. Therefore, it seems that the pathological changes that take place in the brain of AD patients are not limited to neuronal brain tissue and can be detected in peripheral cells as well.…”

Section: Discussionmentioning

confidence: 98%

Age-related changes of apoptotic cell death in human lymphocytes

Schindowski

Leutner

Müller

et al. 2000

Neurobiology of Aging

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Apoptosis seems to be involved in irnmunosenescence associated with aging. Moreover, in lymphocytes (PBL) of patients with Akheimer's disease, an increased susceptibirity to the apoprotic pathway has been described possibly due to impaired protection o f oxidative stress. Accordingly. it seemed to be of particular interest to investigate the contribution of normal aging to the susceptibility from human lymphocytes 20 programmed cell death. We coiild show that PBL from elderly individuals (>60 years) accumuIate apoptosing cells to a significant higher extent in spontaneous and activation-induced cell death compared to younger controls (<35 years). Treatment with the oxidative Stressor 2-deoxy-D-ribose or with agonistic-CD95-antibody pronounced this effect even more implicating a higher sensitivity to reactive oxygen species and a higher functionril CD95 expression, respectively. In addition, expression of the activation markerc HLA-DR and CD95 was significantly increased in CD3 "-cells of aged subjects, while expression of CD25 did not seem to be affected by age.Expression of Bcl-2 was increased in aging and comlated with the number o f apoptotic cells.Kqwordv. &in& Apoptosis: 1,yrnphocytes; Oxidativc stress; dctivation markers; Bcl-2 Programmed cell death (PCD) or apoptosis is of particular interest in aging, as it is thought X o play an irnportant role in various age-related degenerative diseases. Apoptosis of white bIood cells could be one reason for the decrease of the total number of leukocytes and the decrease of the immune response with aging related Z o Cancer, infections, and autoirnmune disorders [3]. Several changes in lymphocytes have been observed related to aging: diminished synthesis of g r o~h and survive factos 146,511, impaired intracellular calcium regulation [18], different surface malecule expression 1431, and defects of signal transdi~ction [36]. Some of these pathological changes are additionally altered in patients witl~ Alzheimer's disease (AD), but are not present in vascular dementia [13][14][15]171. In order to differentiate common and divergent mechanisms of an enhanced susceptibility of lymphocytes to apoptosis in aging and sporadic AD, we investigated in detail the molecular basis of enhanced apoptosis in aged human lymphocytes. Oxidative Stress increases with aging and ltads to enhanced cellular damage (e.g. Iipidperoxidation, protein oxidation, DNA damage (for review see ref.[IO]). In addition, reactive axygen species (ROS) can trigger cells to undergo pragrammed cell death and can act as second rnessenger by influencing transcription factors like NF-KB and AP-I. Increased oxidative stress and decreased ability to cope with ROS could ampliQ apoptotic cell death in aging lymphocytes. BcI-2 acts in an antioxidative and antiapoptotic way and can interfcre with the apoptotic pathway 17,471.One oF the best known and characterized surface receptors related to PCD in lymphocytes is ApollFas (CD95), a rnernber of the himor necrosis factor (W) superfamily. Stimulation of this recep...

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“…We and others (O'Leary et al, 1988;Yen et al, 2000) found no significant changes of the CD4/ CD8 ratio with aging. This is an interesting fact as some neurological disorders (DAT and MS, for instance) show increased CD4/CD8-ratios (Shalit et al, 1995;Crucian et al, 1995b;Schindowski et al, 1999). (means 9S.E.M.).…”

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 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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T Lymphocyte Subpopulations and Activation Markers Correlate with Severity of Alzheimer's Disease

Cited by 89 publications

References 0 publications

Immunophenotypes in the circulation of patients with mild cognitive impairment

Immunophenotypes in the circulation of patients with mild cognitive impairment

Age-related changes of apoptotic cell death in human lymphocytes

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

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