Distinct categories of immunologic changes in frail elderly

Fahey, John L.; Schnelle, Jack F.; Boscardin, John; Thomas, J. K.; Gorre, M.; Aziz, Najib; Sadeghi, Hoss M.; Nishanian, Parunag

doi:10.1016/s0047-6374(00)00094-4

Cited by 71 publications

(62 citation statements)

References 50 publications

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“…The role of interferons in aging is not yet clear. Decreased levels of interferons (IFN-a and -g (Miller, 1980;Lio et al, 2000)) were found by some laboratories while other investigators determined increased levels (Fahey et al, 2000;Sakata-Kaneko et al, 2000;Yen et al, 2000). In addition, our data are in concordance with the latter showing that activated T cells of both subsets from elderly individuals produced more IFNg than from young controls.…”

Section: Discussionsupporting

confidence: 91%

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: Discussionsupporting

confidence: 91%

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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“…Thus, increase of neopterin concentrations concurs with a decline of naive CDS" T-ceils. A similar but statistically not significant inverse rclationship between serum neopterin concentrations and the percentage of CD28* cells among CD8* T-cells of frail elderly has been described by Fahey et al (22). The lack of significance in that study supports the view that there is no overall relationship between increasing neopterin concentrations and the decline of CD28" T-cells, but the decline of the CD45RA" subset is important.…”

Section: Discussionsupporting

confidence: 81%

Increased Neopterin Concentration in Older Age Coincides with Decline of CD28⁺CD45RA⁺ T-cells

et al. 2004

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Neopterin is produced from human monocyte-derived macrophages and dendritic cells upon Stimulation with interferon-y, and increased neopterin concentrations thus indicate cell-mediated immune activation. In healthy individuals increasing neopterin concentrations are found with increasing age, which is also evident from the agedependency of reference values of serum neopterin concentrations. Increase of neopterin concentrations in the elderly may relate to, e.g., altered T lymphocyte differentiation with age. In this study, serum neopterin concentrations of 138 persons (median age: 34 years; interquartile ränge 29.0 -67.8 years) were investigated and compared to age and to the percentage of CD28-CD45RA' or CD28*CD45RO* subsets among CDS* T cells. With increasing age, the percentage of CD28*CD45RA* in CDS" T-cells decreased (Spearman's rank correlation coefficient: r, = -0.561; p < O.OOÜl) accompanied by an increase of the percentage of CD28"CD45RO" in CD8" T-cells (r^ = 4-0.221; p < O.Ol). Serum neopterin concentrations increased with age (fj = -1-0.541; p < 0.0001). This increase of neopterin concentration was accompanied by a decreased percentage of CD28*CD45RA" in CD8* T-cells (rj, = -0.287; p < 0.001). Multivariate analyses revealed that the inverse relationship between the percentage of CD28"'CD45RA"^ in CD8* T-cells and neopterin concentrations was at least partly independent from age. Thus, investigation allows to conclude that an increase of neopterin concentrations with older age is accompanied by a loss of naive CD28*CD45RA' CD8' T-cells. Data suggest that the subset of CD28 CD8" T cells, which is developing in states of sustained immune activation, is important for a chronic production of interferon-y which in turn gives rise to increased neopterin concentrations.

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“…The most prominent immune alteration is occured in T cell comparment. Response of T cells to mitogens weakens and T cell quantity in circulation decreases (Fahey et al, 2000). It is indicated that both circulating CD 4 (+) and CD 8 (+) T cells diminish with aging (Provinciali et al, 2009).…”

Section: Immune Alterationsmentioning

confidence: 99%

“…Besides the changes in cellular level, several alterations appear in cytokin synthesis, which IL-6 levels increase and IL-2 levels decrease in aged individuals (Lesourd & Mazari, 1999). Immune alterations of elderly is shown on Table 2 As a consequence of age related immune alterations, antibody production dimishes and immunological memory shortens (Fahey et al, 2000). Immunologic response to antigens weakens, infections tend to be frequent and heavier with increased age.…”

Section: Immune Alterationsmentioning

confidence: 99%

Encephalitis in Elderly Population

Öztürk¹,

Ege²

2011

Pathogenesis of Encephalitis

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Distinct categories of immunologic changes in frail elderly

Cited by 71 publications

References 50 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

Increased Neopterin Concentration in Older Age Coincides with Decline of CD28⁺CD45RA⁺ T-cells

Encephalitis in Elderly Population

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Distinct categories of immunologic changes in frail elderly

Cited by 71 publications

References 50 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

Increased Neopterin Concentration in Older Age Coincides with Decline of CD28+CD45RA+ T-cells

Encephalitis in Elderly Population

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Increased Neopterin Concentration in Older Age Coincides with Decline of CD28⁺CD45RA⁺ T-cells