Impaired in vivo CD4+ T cell expansion and differentiation in aged mice is not solely due to T cell defects: Decreased stimulation by aged dendritic cells

Pereira, Luciana; Souza, Ana Paula Duarte de; Borges, Thiago J.; Bonorino, Cristina

doi:10.1016/j.mad.2011.03.005

Cited by 61 publications

(60 citation statements)

References 54 publications

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“…In this way, a blockade of the CD40 costimulatory pathway is one of the most successful means of inhibiting an alloreactive T-cell response, as demonstrated for allografts (71), a strategy which could be compared to that used by the parasite. The same impairment of the CD4 ϩ T-cell response was, curiously, described in aging, resulting in susceptibility to infections and cancer (72). The same phenotypic parameters, lower levels of MHC-peptide complex expression and reduced CD40 levels (72), were observed, as if trypanosome infection induced preaging of the host immune system.…”

Section: Discussionmentioning

confidence: 71%

The Trypanosoma brucei gambiense Secretome Impairs Lipopolysaccharide-Induced Maturation, Cytokine Production, and Allostimulatory Capacity of Dendritic Cells

et al. 2013

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bTrypanosoma brucei gambiense, a parasitic protozoan belonging to kinetoplastids, is the main etiological agent of human African trypanosomiasis (HAT), or sleeping sickness. One major characteristic of this disease is the dysregulation of the host immune system. The present study demonstrates that the secretome (excreted-secreted proteins) of T. b. gambiense impairs the lipopolysaccharide (LPS)-induced maturation of murine dendritic cells (DCs). The upregulation of major histocompatibility complex class II, CD40, CD80, and CD86 molecules, as well as the secretion of cytokines such as tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-6, which are normally released at high levels by LPS-stimulated DCs, is significantly reduced when these cells are cultured in the presence of the T. b. gambiense secretome. Moreover, the inhibition of DC maturation results in the loss of their allostimulatory capacity, leading to a dramatic decrease in Th1/Th2 cytokine production by cocultured lymphocytes. These results provide new insights into a novel efficient immunosuppressive mechanism directly involving the alteration of DC function which might be used by T. b. gambiense to interfere with the host immune responses in HAT and promote the infectious process.

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Section: Discussionmentioning

confidence: 71%

The Trypanosoma brucei gambiense Secretome Impairs Lipopolysaccharide-Induced Maturation, Cytokine Production, and Allostimulatory Capacity of Dendritic Cells

et al. 2013

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“…Learning can be quantified by changes in behavioural performance (Pereira et al, 2011;Andree & Maitra, 2002). A participant can demonstrate learning by showing a change in performance in line with a trained behaviour.…”

Section: Behavioural Performancementioning

confidence: 99%

“…reported that older adults who demonstrated reduced cross-limb transfer following training on a simple task nonetheless exhibited comparable transfer to young adults after training on a complex grip and lift task. In contrast, task complexity does not seem a determining factor with young adults, who show transfer following training on ballistic finger abductions , maze tracing (Van Mier & Petersen, 2006), dexterity and precision tasks (Pereira et al, 2011), visuomotor adaptation (Pan & Gemmert, 2013) and object weight adaptation . It is well established that undertaking simple and complex tasks draws upon differential neural circuitry Holmstrom et al, 2011;Mima et al, 1999;Sadato et al, 1996;Solodkin et al, 2001;Verstynen et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Is plasticity in the human motor cortices altered in healthy older adults?

Dickins¹

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Neuroplasticity refers to the ability of the brain to alter its structure and function in response to the demands of its environment. Substantial evidence from studies in non-human animals suggests that neuroplasticity at the synaptic level is reduced in the aged brain. In humans, ageing is associated with cognitive and motor decline and some experimental evidence using non-invasive brain stimulation and motor training suggests that neuroplasticity is reduced in the motor cortex. It is also evident, however, that there is variability in age-related decline of motor performance and neuroplasticity across individuals. In the studies investigating neuroplasticity, little consideration has been given to changes occurring outside the targeted region, for example in homotopic regions of the contralateral hemisphere. This is an important limitation, as neuroimaging studies suggest that older adults exhibit more widespread activity both within and across the cerebral hemispheres, relative to young adults, when performing the same motor task. This finding suggests that additional neural populations may be recruited in older adults to assist in learning new motor skills. The aim of this thesis then, was to investigate whether the manifestation of neuroplasticity across the cerebral hemispheres is altered in older adults. To achieve this, three different protocols using skilled training or non-invasive brain stimulation were employed to experimentally induce neuroplasticity primarily in the primary motor cortex (M1). These protocols have been shown to induce changes with characteristics that resemble long-term potentiation (LTP) and long-term depression (LTD) in animal models, which is the candidate mechanism for synaptic plasticity. In each study neuroplasticity effects were probed by measuring changes in corticospinal excitability in bilateral coritcospinal pathways (corticospinal plasticity) using single-pulse transcranial magnetic stimulation (TMS) and motor-evoked potentials (MEPs).In the first study young and older participants were trained on a simple and complex motor task.The degree to which performance improvement transferred from the trained to the untrained hand and the extent to which this reflected changes in the distribution of corticospinal plasticity across the hemispheres were assessed. Both groups demonstrated performance improvements in the trained and untrained hand, although performance improvement in the trained hand was smaller in older adults. The percentage transfer from the trained to the untrained hand was comparable between young and older adults. Importantly, after training on the simple task, corticospinal excitability increased bilaterally in both young and older adults, a similar trend was also observed with the complex task. This result indicates that corticospinal plasticity, its manifestation in bilateral corticospinal pathways, and its relation to behavioural performance was comparable between young and older adults.iii In a second study, intermittent theta burst stimulation (iT...

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“…diminished capacity of DC [110]. Signal transduction in human T cells from elderly was reduced by a defect in tyrosine phosphorylation of CD3 (TCR), CD4, CD8 or IL-2R [111] and by an altered cell membrane fluidity [13].…”

Section: Lymphocytesmentioning

confidence: 99%

“…In aged mice, an altered distribution of DC subsets was found as well [608]. Phagocytosis, pinocytosis, migration and chemotaxis were impaired in DC from aged donors, leading to a decreased ability to present antigens [63,110,603,609]. As a result, aged DC have a reduced ability to stimulate T cell responses, and are less able to control tumor growth [110,609,610].…”

Section: And Agingmentioning

confidence: 99%

The aging immune system and nutritional interventions

Beek

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Impaired in vivo CD4+ T cell expansion and differentiation in aged mice is not solely due to T cell defects: Decreased stimulation by aged dendritic cells

Cited by 61 publications

References 54 publications

The Trypanosoma brucei gambiense Secretome Impairs Lipopolysaccharide-Induced Maturation, Cytokine Production, and Allostimulatory Capacity of Dendritic Cells

The Trypanosoma brucei gambiense Secretome Impairs Lipopolysaccharide-Induced Maturation, Cytokine Production, and Allostimulatory Capacity of Dendritic Cells

Is plasticity in the human motor cortices altered in healthy older adults?

The aging immune system and nutritional interventions

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