IL‐15 preferentially enhances functional properties and antigen‐specific responses of CD4+CD28<sup>null</sup> compared to CD4+CD28+ T cells

Alonso-Arias, Rebeca; Moro-García, Marco Antonio; Vidal-Castiñeira, José Ramón; Solano-Jaurrieta, Juan José; Suárez-García, Francisco Manuel; Coto, Eliécer; López‐Larrea, Carlos

doi:10.1111/j.1474-9726.2011.00725.x

Cited by 26 publications

(44 citation statements)

References 55 publications

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“…Despite the high levels of anti-CMV antibodies and the high frequencies of CD28 null T cells, we found no association between CMV infection and TNF-␣ levels in the sera of elderly individuals. There was a significant correlation with the level of IL-15, another cytokine implicated in the loss of CD28 expression in CD8 ϩ T cells and an inducer of preferential proliferation and functional capabilities of CD4 ϩ CD28 null T cells (20,37).…”

Section: Cd28mentioning

confidence: 90%

Intensity of the Humoral Response to Cytomegalovirus Is Associated with the Phenotypic and Functional Status of the Immune System

Alonso-Arias

Moro-García

Echeverría

et al. 2013

J Virol

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Cytomegalovirus (CMV) infection exerts an enormous effect on human immunity, as it is associated with an immune-impaired response, a variety of chronic diseases, and overall survival in elderly individuals. Levels of anti-CMV antibodies may be associated with the differentiation degree of T cell subsets. Titers are significantly higher in the elderly and positively correlated with specific CD4؉ T cell responses to CMV. In the elderly, antibody titers are associated with the degree of differentiation and the T cell receptor excision circle (TREC) content in CD4؉ T cells, with other features of the immune risk profile, and with a reduced ability to respond to immunization in vivo. Associations may be absent in young subjects because their anti-CMV antibody titers are lower than those of the elderly. However, comparing young and elderly individuals with similar antibody levels reveals differences in their highly differentiated and naïve T cells. These are more marked in individuals with high titers. In parallel with the increase in anti-CMV antibodies, the elderly experience a significant reduction in absolute counts of naïve CD4؉ T cells, which may be a strategy to compensate for the expansion of differentiated cells and to avoid an increase in total T cells. In summary, our results show that titers of anti-CMV antibodies, and not only CMV seropositivity, are related to differentiation status and immunocompetence in the elderly, making this as an important prognostic marker of the status of immune system function.T he betaherpesvirus cytomegalovirus (CMV) is a persistent activating virus that primarily resides in the myeloid cell compartment but also spreads to other cell types. Clinically, infection is considered essentially asymptomatic in immunocompetent hosts. However, immunosuppressed individuals may suffer serious consequences as a result of viral reemergence. After infection, the virus establishes lifelong latency within the host and periodically reactivates. Reactivation from latency is a key step in the pathogenesis of the infection and can be detected in response to inflammation, infection, stress, or immunosuppression (1, 2). Activation of protein kinase C and NF-B by tumor necrosis factor alpha (TNF-␣) and increasing concentrations of cyclic AMP by stress hormones and prostaglandins promote viral reactivation and replication. Reactivation of CMV is more frequent in the elderly, as demonstrated by the direct detection of CMV DNA in the urine. Although reactivation is frequent in the elderly, it is subclinical in nature (3).Recently, CMV has been linked to a variety of chronic diseases with an inflammatory component, including cardiovascular diseases, cancer, and cognitive and functional impairment (4-7). The specific mechanisms responsible for these associations have not been fully determined but are likely to have an inflammatory and immune component. Reactivation may result in increased levels of proinflammatory molecules such as interleukin 6 (IL-6), TNF-␣, and C-reactive protein (CRP). In fact, CMV ...

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Section: Cd28mentioning

confidence: 90%

Intensity of the Humoral Response to Cytomegalovirus Is Associated with the Phenotypic and Functional Status of the Immune System

Alonso-Arias

Moro-García

Echeverría

et al. 2013

J Virol

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“…Recent updates showed that IL-15 preferentially supports proliferation of CD28 null CD4 + T cells over the CD28 + CD4 + T cells. IL-15 not only supports proliferation, but enhances the cytotoxic activity in a shortterm manner by increased IFN-g, granzyme B and perforin production [89]. Other studies supported the differential susceptibility of CD28 null versus CD28 + T cells to other stimuli including cytokines such as IL-12 that may drive Th1 versus Th2 responses.…”

Section: Restoring Immunitymentioning

confidence: 94%

The Immune System in the Elderly: A Fair Fight Against Diseases?

et al. 2013

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The immune system is a very dynamic network, consisting of various innate and adaptive cells acting via direct cell-cell contact, as well as indirect messaging mediated by soluble factors. Changes in the number or quality of receptors involved in these events alter the capacity of the immune system to respond properly. There is an increasing awareness that many chronic infections and diseases, such as cytomegalovirus, impact on the immune system. Concurrently, there are changes in immune profiles of healthy, as well as ill, elderly individuals. All these changes translate into obvious signs of immunological aging that are more profound in diseases. This review will discuss the manifestation of different diseases in the elderly and how the immune system behaves in such situations.

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“…CD4 + CD28 − T cells also show no association with antibodies to anti-citrullinated protein, another putative autoantigen in RA, in the serum or synovial fluid (435152). Moreover, accumulating evidence demonstrates that chronic stimulation with proinflammatory cytokines such as TNF-α and IL-15 is responsible for the expansion of CD4 + CD28 − T cells in humans (205354). …”

Section: Clinical Relevance Of Cd4+cd28− T Cellsmentioning

confidence: 99%

Unusual CD4⁺CD28⁻T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

Lee

2016

Immune Netw

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CD28 is a primary co-stimulatory receptor that is essential for successful T cell activation, proliferation, and survival. While ubiquitously expressed on naive T cells, the level of CD28 expression on memory T cells is largely dependent on the T-cell differentiation stage in humans. Expansion of circulating T cells lacking CD28 was originally considered a hallmark of age-associated immunological changes in humans, with a progressive loss of CD28 following replicative senescence with advancing age. However, an increasing body of evidence has revealed that there is a significant age-inappropriate expansion of CD4+CD28− T cells in patients with a variety of chronic inflammatory diseases, suggesting that these cells play a role in their pathogenesis. In fact, expanded CD4+CD28− T cells can produce large amounts of proinflammatory cytokines such as IFN-γ and TNF-α and also have cytotoxic potential, which may cause tissue damage and development of pathogenesis in many inflammatory disorders. Here we review the characteristics of CD4+CD28− T cells as well as the recent advances highlighting the contribution of these cells to several disease conditions.

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IL‐15 preferentially enhances functional properties and antigen‐specific responses of CD4+CD28^null compared to CD4+CD28+ T cells

Abstract: SummaryOne of the most prominent changes during T-cell aging in humans is the accumulation of CD28 null T cells, mainly CD8+ and also CD4+

Cited by 26 publications

References 55 publications

Intensity of the Humoral Response to Cytomegalovirus Is Associated with the Phenotypic and Functional Status of the Immune System

Intensity of the Humoral Response to Cytomegalovirus Is Associated with the Phenotypic and Functional Status of the Immune System

The Immune System in the Elderly: A Fair Fight Against Diseases?

Unusual CD4⁺CD28⁻T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

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IL‐15 preferentially enhances functional properties and antigen‐specific responses of CD4+CD28null compared to CD4+CD28+ T cells

Abstract: SummaryOne of the most prominent changes during T-cell aging in humans is the accumulation of CD28 null T cells, mainly CD8+ and also CD4+

Cited by 26 publications

References 55 publications

Intensity of the Humoral Response to Cytomegalovirus Is Associated with the Phenotypic and Functional Status of the Immune System

Intensity of the Humoral Response to Cytomegalovirus Is Associated with the Phenotypic and Functional Status of the Immune System

The Immune System in the Elderly: A Fair Fight Against Diseases?

Unusual CD4+CD28−T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders

Contact Info

Product

Resources

About

IL‐15 preferentially enhances functional properties and antigen‐specific responses of CD4+CD28^null compared to CD4+CD28+ T cells

Unusual CD4⁺CD28⁻T Cells and Their Pathogenic Role in Chronic Inflammatory Disorders