Experimental Expansion of the Regulatory T Cell Population Increases Resistance to African Trypanosomiasis

Guilliams, Martin; Bosschaerts, Tom; Hérin, Michel; Hünig, Thomas; Loi, Patrizia; Flamand, Véronique; Baetseĺier, Patrick De; Beck, Alain

doi:10.1086/590439

Cited by 45 publications

(65 citation statements)

References 47 publications

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“…In the present study, we tested a more powerful and less pleiotropic approach of boosting Treg compared with histone deacetylase inhibition-stimulation with the CD28SA. Similar to previous studies in healthy mice 13 and various disease models, [15][16][17][18][19] CD28SA substantially increased the number of Treg in the periphery as well as in the brain. CD28SA …”

Section: Discussionsupporting

confidence: 87%

Amplification of Regulatory T Cells Using a CD28 Superagonist Reduces Brain Damage After Ischemic Stroke in Mice

Mracskó

Liesz

et al. 2015

Stroke

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Background and Purpose-Neuroinflammation plays an important role in ischemic brain injury. Regulatory T cells (Treg) are important endogenous immune modulators. We tested the hypothesis that Treg amplification with a CD28 superagonistic monoclonal antibody (CD28SA) reduces brain damage in murine cerebral ischemia. Methods-Cerebral ischemia was induced by coagulation of the distal middle cerebral artery or by 60 minutes filament occlusion of the proximal middle cerebral artery in C57BL6 mice. 150 μg CD28SA was injected intraperitoneally 3 or 6 hours after ischemia onset. Outcome was determined by infarct volumetry and behavioral testing. Brain-infiltrating leukocyte subpopulations were analyzed by flow cytometry and immunohistochemistry 3 and 7 days after middle cerebral artery occlusion. Results-CD28SA reduced infarct size in both models and attenuated functional deficit 7 days after stroke induction. Mice treated with CD28SA increased numbers of Treg in spleen and brain. Tregs were functionally active and migrated into the brain where they accumulated and proliferated in the peri-infarct area. More than 60% of brain infiltrating Treg produced interleukin-10 in CD28SA compared with 30% in control. Conclusions-In

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Section: Discussionsupporting

confidence: 87%

Amplification of Regulatory T Cells Using a CD28 Superagonist Reduces Brain Damage After Ischemic Stroke in Mice

Mracskó

Liesz

et al. 2015

Stroke

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“…Most studies assessed the development of anaemia by looking at the red blood cell (RBC) counts at different time points in experimentally infected mice, and comparing these counts to preinfection levels or those of controls (uninfected mice) 11,21,22 . This assessment assumes that preinfection levels were normal, with anaemia being defined as a drop in RBC count by a specified magnitude.…”

Section: Diagnosis Of Anaemia In African Trypanosomiasismentioning

confidence: 99%

Role of Cytokines in <i>Trypanosoma brucei</i>-Induced Anaemia: A Review of the Literature

Musaya¹,

Matovu²,

Nyirenda³

et al. 2015

Mal. Med. J

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BackgroundAnaemia is an important complication of trypanosomiasis. The mechanisms through which trypanosomal infection leads to anaemia are poorly defined. A number of studies have implicated inflammatory cytokines, but these data are limited and inconsistent. In this article, we reviewed the published literature on cytokines associated with Trypanosoma brucei infections and their role in the immunopathology leading to anaemia. MethodologyArticles were searched in PubMed through screening of titles and abstracts with no limitation on date of publishing and study design. Articles in English were searched using keywords "African trypanosomiasis", "sleeping sickness", "Trypanosoma brucei", in all possible combinations with "anaemia" and/or "cytokines". ResultsTwelve articles examining cytokines and their role in trypanosomeinduced anaemia were identified out of 1095 originally retrieved from PubMed. None of the articles identified were from human-based studies. A total of eight cytokines were implicated, with four cytokines (IFN-γ, IL-10, TNF-α, IL-12) showing an association with anaemia. These articles reported that mice lacking TNF-α were able to control anaemia, and that IFN-γ was linked to severe anaemia given its capacity to suppress erythropoiesis, while IL-10 was shown to regulate IFN-γ and TNF-α, providing a balance that was associated with severity of anaemia. IFN-γ and TNF-α have also been reported to work in concert with other factors such as nitric oxide and iron in order to induce anaemia. ConclusionIFN-γ, IL-10, and TNF-α were the three major cytokines identified to be heavily involved in anaemia caused by Trypanosoma brucei infection. The anti-inflammatory cytokine, IL-10, was shown to counter the effects of proinflammatory cytokines in order to balance the severity of anaemia. The mechanism of anaemia is multifactorial and therefore requires further, more elaborate research. Data from human subjects would also shed more light.

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“…ϩ naturally occurring regulatory T cells (14,15) as well as alternatively activated monocytic cells (M2) (16) can protect the host via the production of IL-10. On the other side, a particular subset of MHC-II-restricted socalled "pathogenic" CD4 ϩ T cells producing IFN-␥ has been suggested to contribute to early mortality of infected hosts (11).…”

Section: Foxp3mentioning

confidence: 99%

“…Parasitemia was monitored by tail blood puncture. Spleen and liver nonparenchymal cells were isolated as described previously (14,15). Experiments were performed in compliance with the relevant laws and institutional guidelines.…”

Section: Parasites Mice and Infectionsmentioning

confidence: 99%

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IL-10 Dampens TNF/Inducible Nitric Oxide Synthase-Producing Dendritic Cell-Mediated Pathogenicity during Parasitic Infection

Guilliams

Movahedi

Bosschaerts

et al. 2009

The Journal of Immunology

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156

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Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells are assumed to be the major source of TNF and NO during Trypanosoma brucei brucei infection, their cellular origin remains unclear. In this study, we show that bone marrow-derived monocytes accumulate and differentiate to TNF/inducible NO synthase-producing dendritic cells (TIP-DCs) in the spleen, liver, and lymph nodes of T. brucei brucei-infected mice. Although TIP-DCs have been shown to play a beneficial role in the elimination of several intracellular pathogens, we report that TIP-DCs, as a major source of TNF and NO in inflamed organs, could contribute actively to tissue damage during the chronic stage of T. brucei brucei infection. In addition, the absence of IL-10 leads to enhanced differentiation of monocytes to TIP-DCs, resulting in exacerbated pathogenicity and early death of the host. Finally, we demonstrate that sustained production of IL-10 following IL-10 gene delivery treatment with an adeno-associated viral vector to chronically infected mice limits the differentiation of monocytes to TIP-DCs and protects the host from tissue damage.

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Experimental Expansion of the Regulatory T Cell Population Increases Resistance to African Trypanosomiasis

Cited by 45 publications

References 47 publications

Amplification of Regulatory T Cells Using a CD28 Superagonist Reduces Brain Damage After Ischemic Stroke in Mice

Amplification of Regulatory T Cells Using a CD28 Superagonist Reduces Brain Damage After Ischemic Stroke in Mice

Role of Cytokines in <i>Trypanosoma brucei</i>-Induced Anaemia: A Review of the Literature

IL-10 Dampens TNF/Inducible Nitric Oxide Synthase-Producing Dendritic Cell-Mediated Pathogenicity during Parasitic Infection

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