Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells

Tarazona, Raquel; DelaRosa, Olga; Alonso, Corona; Ostos, Belén; Espejo, Joaquı́n; Peña, José; Solana, Rafael

doi:10.1016/s0047-6374(00)00199-8

Cited by 215 publications

(173 citation statements)

References 56 publications

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“…Consistent with previous reports indicating increased numbers of CD56ϩ T cells in elderly persons (particularly centenarians) (47), our data show that healthy persons ages Ն39 years have a significantly higher frequency of these cells than younger individuals. In contrast, there is an even higher level of in vivo accumulation of CD56ϩ T cells among RA patients, which is disproportionate with age.…”

Section: Discussionsupporting

confidence: 93%

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Michel

Turesson

Lemster

et al. 2007

Arthritis & Rheumatism

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Objective. T cells deficient in CD28 expression have been implicated in the pathogenesis of rheumatoid arthritis (RA). Given that CD28-null T cells are functionally heterogeneous, we undertook this study to screen for novel receptors on these cells.Methods. Seventy-two patients with RA (ages 35-84 years) and 53 healthy persons (32 young controls ages 19-34 years, 21 older controls ages 39-86 years) were recruited. Phenotypes and proliferative capacity of T cells from fresh leukocytes and of long-term cultures were monitored by flow cytometry. Lung biopsy specimens from patients with RA-associated interstitial pneumonitis (IP) were examined by immunohistochemistry. Receptor functionality was assessed by crosslinking bioassays.Results. Chronic stimulation of CD28؉ T cells in vitro yielded progenies that lacked CD28 but that gained CD56. Ex vivo analysis of leukocytes from patients with extraarticular RA showed a higher frequency of CD56؉,CD28-null T cells than in patients with disease confined to the joints or in healthy controls. CD56؉,CD28-null T cells had nil capacity for proliferation, consistent with cellular senescence. CD56؉ T cells had skewed T cell receptor (TCR) ␣/␤-chain usage and restricted TCR third complementarity-determining region spectra. Histologic studies showed that CD56؉ T cells were components of cellular infiltrates in RAassociated IP. CD56 crosslinking on T cells sufficiently induced cytokine production, although CD56/TCR coligation induced higher production levels.Conclusion. Chronic activation of T cells induces counterregulation of CD28 and CD56 expression. The loss of CD28 is accompanied by the gain of CD56 that confers TCR-independent and TCR-dependent activation pathways. We propose that accumulation of CD56؉ T cells in RA contributes to maladaptive immune responses and that CD56؉ T cells are potential targets for therapy.

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Section: Discussionsupporting

confidence: 93%

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

Michel

Turesson

Lemster

et al. 2007

Arthritis & Rheumatism

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“…However, the role of CD161 expression in chronically activated CD8 T cytotoxic cells in the mouse (75) and humans (36,76,77) has not been elucidated. Nevertheless, given the expression on effector/senescent T cells, which display decreased functional activity (37), it likely functions to negatively influence cytotoxic activity.…”

Section: Discussionmentioning

confidence: 99%

“…This C-type lectin expressed on NK T cells has costimulatory activity (35), which may also be the same for activated CTL. In HIV-1 infection, the number of CD28 Ϫ CD8 ϩ peripheral T cells expressing NK markers such as CD161 is increased (36), likely due to the chronic activation state of the immune system as observed in other viral diseases, autoimmunity, cancers, and in the elderly (37).…”

mentioning

confidence: 99%

TCRγδ+ and CD161+ Thymocytes Express HIV-1 in the SCID-hu Mouse, Potentially Contributing to Immune Dysfunction in HIV Infection

Gurney

Yang

Wilson

et al. 2002

The Journal of Immunology

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The vast diversity of the T cell repertoire renders the adaptive immune response capable of recognizing a broad spectrum of potential antigenic peptides. However, certain T cell rearrangements are conserved for recognition of specific pathogens, as is the case for TCRγδ cells. In addition, an immunoregulatory class of T cells expressing the NK receptor protein 1A (CD161) responds to nonpeptide Ags presented on the MHC-like CD1d molecule. The effect of HIV-1 infection on these specialized T cells in the thymus was studied using the SCID-hu mouse model. We were able to identify CD161-expressing CD3+ cells but not the CD1d-restricted invariant Vα24/Vβ11/CD161+ NK T cells in the thymus. A subset of TCRγδ cells and CD161-expressing thymocytes express CD4, CXCR4, and CCR5 during development in the thymus and are susceptible to HIV-1 infection. TCRγδ thymocytes were productively infectable by both X4 and R5 virus, and thymic HIV-1 infection induced depletion of CD4+ TCRγδ cells. Similarly, CD4+CD161+ thymocytes were depleted by thymic HIV-1 infection, leading to enrichment of CD4−CD161+ thymocytes. Furthermore, compared with the general CD4-negative thymocyte population, CD4−CD161+ NK T thymocytes exhibited as much as a 27-fold lower frequency of virus-expressing cells. We conclude that HIV-1 infection and/or disruption of cells important in both innate and acquired immunity may contribute to the overall immune dysfunction seen in HIV-1 disease.

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“…We have studied CD4+ and CD8+ subsets investigating the expression of the isoforms of CD45 (CD45RA and CD45RO), which can be informative for the differentiation stage of T cells (Michie et al, 1992;Sallusto et al, 1999), and the expression of two major positive T cell costimulatory receptors CD27 and CD28 and two negative receptors expressed by late-stage differentiated cells, CD57 and KLRG1 (sometimes referred to as markers of "senescence"). CD57 is expressed on NK cells and late-stage CD8+ T cells with slight expression on CD4+ cells sometimes reported (Tarazona et al, 2000;Ibegbu et al, 2005), whereas KLRG1 is the Killer Lectin receptor G1, expressed on larger proportions of CD4+ T cells as well as CD8+ T cells and NK cells. It was initially suggested that the expression of KLRG-1 marked replicatively-senescent cells (Voehringer et al, 2001;Voehringer et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Immune profiling of Alzheimer patients

Pellicanò

Larbi

Goldeck

et al. 2012

Journal of Neuroimmunology

126

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Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the disease.

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Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells

Cited by 215 publications

References 56 publications

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

CD56‐expressing T cells that have features of senescence are expanded in rheumatoid arthritis

TCRγδ+ and CD161+ Thymocytes Express HIV-1 in the SCID-hu Mouse, Potentially Contributing to Immune Dysfunction in HIV Infection

Immune profiling of Alzheimer patients

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