Cellular aging and senescence characteristics of human T-lymphocytes

Onyema, Oscar Okwudiri; Njemini, Rose; Bautmans, Ivan; Renmans, Wim; Waele, Marc De; Mets, Tony

doi:10.1007/s10522-011-9366-z

Cited by 42 publications

(51 citation statements)

References 61 publications

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“…Although CD28-deficient T cells may contribute to control viral infection, the elevation of CD28 2 CD8 + T cells is generally seen as a significant predictor of immune senescence (5,17,46). Moreover, CD28…”

Section: Cd28mentioning

confidence: 99%

CD58/CD2 Is the Primary Costimulatory Pathway in Human CD28−CD8+ T Cells

Leitner

Herndler‐Brandstetter

Zlabinger

et al. 2015

The Journal of Immunology

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A substantial proportion of CD8+ T cells in adults lack the expression of the CD28 molecule, and the aging of the immune system is associated with a steady expansion of this T cell subset. CD28−CD8+ T cells are characterized by potent effector functions but impaired responses to antigenic challenge. CD28 acts as the primary T cell costimulatory receptor, but there are numerous additional receptors that can costimulate the activation of T cells. In this study, we have examined such alternative costimulatory pathways regarding their functional role in CD28−CD8+ T cells. Our study showed that most costimulatory molecules have a low capacity to activate CD28-deficient T cells, whereas the engagement of the CD2 molecule by its ligand CD58 clearly costimulated proliferation, cytokine production, and effector function in this T cell subset. CD58 is broadly expressed on APCs including dendritic cells. Blocking CD58 mAb greatly reduced the response of human CD28−CD8+ T cells to allogeneic dendritic cells, as well as to viral Ags. Our results clearly identify the CD58/CD2 axis as the primary costimulatory pathway for CD8 T cells that lack CD28. Moreover, we show that engagement of CD2 amplifies TCR signals in CD28−CD8+ T cells, demonstrating that the CD2–CD58 interaction has a genuine costimulatory effect on this T cell subset. CD2 signals might promote the control of viral infection by CD28−CD8+ T cells, but they might also contribute to the continuous expansion of CD28−CD8+ T cells during chronic stimulation by persistent Ag.

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Section: Cd28mentioning

confidence: 99%

CD58/CD2 Is the Primary Costimulatory Pathway in Human CD28−CD8+ T Cells

Leitner

Herndler‐Brandstetter

Zlabinger

et al. 2015

The Journal of Immunology

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“…In addition, repeated antigenic challenge through life leads to telomere shortening in lymphocytes (Akbar et al 2004), thus compromising immune memory. T cells from aged donors are also prone to autoimmune reactions as they lose expression of the co-stimulatory molecules CD28 and express markers normally associated with NK cells, such as NKG2D (Alonso-Arias et al 2011) and KLRG1 (Onyema et al 2012), which allow activation by selfantigens.…”

Section: Mdscs Immunosenescence and Ageingmentioning

confidence: 99%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.

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“…In their study the expression of CD57 on T-cells was related to short telomeres and loss of proliferation capacity, possibly linking its presence to senescence (Brenchley et al, 2003). CD28+CD57+ T-cells differ from the more prevalent CD28ÀCD57+ cells, which are known to correspond to a highly differentiated subpopulation with effector function (Onyema et al, 2012). While CD28ÀCD57+ cells have been related to persistent viral infections and an immune risk profile (IRP) (Olsson et al, 2000;Wikby et al, 2002), we have found that CMV seropositivity was not related to the prevalence of CD28+CD57+ cells (Onyema et al, 2012).…”

Section: Introductionmentioning

confidence: 96%

“…In elderly compared with young persons, we have observed not only a higher prevalence of CD28ÀCD57+ cells, as expected, but also of a small subpopulation that is CD28+CD57+. (Onyema et al, 2012). The attention on CD28+CD57+ cells was first drawn in 2003 by Brenchley et al, who observed in six healthy individuals that 8% of memory CD8+ T cells consisted of the CD28 +CD57+ phenotype.…”

Section: Introductionmentioning

confidence: 99%