A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence

Mamedov, Murad R.; Scholzen, Anja; Nair, Ramesh V.; Cumnock, Katherine; Kenkel, Justin A.; Oliveira, José Henrique M.; Trujillo, Damian L.; Saligrama, Naresha; Zhang, Yue; Rubelt, Florian; Schneider, David; Chien, Yueh‐hsiu; Sauerwein, Robert W.; Davis, Mark M.

doi:10.1016/j.immuni.2018.01.009

Cited by 99 publications

(131 citation statements)

References 60 publications

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“…To explain this discrepancy, we hypothesized that cd T cells might affect humoral immunity by orchestrating other immune cells, such as natural killer cells. 25 In comparison, in this report, we found that Vc1 + Vd6.3 À cd T cells are present during infection and in the naive condition. Moreover, it is possible that cd T cells have some effects on fibroblastic reticular cells, causing the formation of a GC in the spleen for the development of humoral immunity during the early phase of infection.…”

Section: Discussionmentioning

confidence: 42%

“…25 The M-CSF-producing Vd6.3 + cd T cells were necessary for preventing the parasitaemic recrudescence of P. chabaudi. 25 The M-CSF-producing Vd6.3 + cd T cells were necessary for preventing the parasitaemic recrudescence of P. chabaudi.…”

Section: Pbxat Infectionmentioning

confidence: 99%

“…A recent study showed that Vd6.3 + cd T cells expanded clonally and expressed M-CSF. 25 The M-CSF-producing Vd6.3 + cd T cells were necessary for preventing the parasitaemic recrudescence of P. chabaudi. Therefore, we investigated whether the cytokine production differed among the cd T-cell subsets (Fig.…”

Section: Cytokine Gene Expression By Vc1 + Vd63 + CD T Cells Was Simmentioning

confidence: 99%

“…Therefore, the fluctuations in the parasitaemia of bloodstage PbXAT parasites are strongly related to IFN-c. 25 Therefore, it will be interesting to determine whether the Vd6.3 + cd T cells are the same as, or a different subset of, Vc1 + cd T cells in terms of their ability to produce cytokines. cd T cells elicit dendritic cell activation via CD40 ligand expression during PbXAT infection, resulting in induction of adequate Th1 cell differentiation for protection against parasites.…”

Section: Introductionmentioning

confidence: 99%

“…The M-CSF-producing Vd6.3 + cd T cells function to prevent parasitaemia recrudescence. 25 Therefore, it will be interesting to determine whether the Vd6.3 + cd T cells are the same as, or a different subset of, Vc1 + cd T cells in terms of their ability to produce cytokines. Previously, we found that anti-TCR-cd monoclonal antiobody (mAb) -treated mice had reduced levels of some isotypes of malaria-specific antibodies during the late phase of infection.…”

Section: Introductionmentioning

confidence: 99%

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γδ T cells modulate humoral immunity against Plasmodium berghei infection

et al. 2018

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It is unclear whether γδ T cells are involved in humoral immunity against Plasmodium infection. Here, we show that B-cell-immunodeficient mice and γδ T-cell-deficient mice were incapable of protecting against Plasmodium berghei XAT parasites. γδ T-cell-deficient mice developed reduced levels of antigen-specific antibodies during the late phase of infection. The numbers of follicular helper T cells and germinal centre B cells in γδ T-cell-deficient mice were lower than in wild-type mice during the late phase of infection. Expression profiling of humoral immunity-related cytokines in γδ T cells showed that interleukin-21 (IL-21) and interferon-γ (IFN-γ) are increased during the early stage of infection. Furthermore, blockade of IL-21 and IFN-γ signalling during the early stage of infection led to reduction in follicular helper T cells and germinal centre B cells. γδ T-cell production of IL-21 and IFN-γ is crucial for the development and maintenance of follicular helper T cells and germinal centre B cells during the late phase of infection. Our data suggest that γδ T cells modulate humoral immunity against Plasmodium infection.

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Section: Discussionmentioning

confidence: 42%

Section: Pbxat Infectionmentioning

confidence: 99%

Section: Cytokine Gene Expression By Vc1 + Vd63 + CD T Cells Was Simmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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γδ T cells modulate humoral immunity against Plasmodium berghei infection

et al. 2018

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Peripheral γδ T Cells Regulate Neutrophil Expansion and Recruitment in Experimental Psoriatic Arthritis

Nguyen

Furuya

Das

et al. 2022

Arthritis & Rheumatology

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Objective. This study was undertaken to identify the mechanistic role of γδ T cells in the pathogenesis of experimental psoriatic arthritis (PsA).Methods. In this study, we performed interleukin-23 (IL-23) gene transfer in wild-type (WT) and T cell receptor δ-deficient (TCRδ −/− ) mice and conducted tissue phenotyping in the joint, skin, and nails to characterize the inflammatory infiltrate. We further performed detailed flow cytometry, immunofluorescence staining, RNA sequencing, T cell repertoire analysis, and in vitro T cell polarization assays to identify regulatory mechanisms of γδ T cells.Results. We demonstrated that γδ T cells support systemic granulopoiesis, which is critical for murine PsA-like pathology. Briefly, γδ T cell ablation inhibited the expression of neutrophil chemokines CXCL1 and CXCL2 and neutrophil CD11b+Ly6G+ accumulation in the aforementioned PsA-related tissues. Although significantly reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A was detected systemically in TCRδ −/− mice, no GM-CSF+/IL-17A+ γδ T cells were detected locally in the inflamed skin or bone marrow in WT mice. Our data showed that nonresident γδ T cells regulate the expansion of an CD11b+Ly6G+ neutrophil population and their recruitment to joint and skin tissues, where they develop hallmark pathologic features of human PsA.Conclusion. Our findings do not support the notion that tissue-resident γδ T cells initiate the disease but demonstrate a novel role of γδ T cells in neutrophil regulation that can be exploited therapeutically in PsA patients.

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Resolving the mystery—How TCR transgenic mouse models shed light on the elusive case of gamma delta T cells

Hahn

Winkler

2020

Journal of Leukocyte Biology

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Cutting‐edge questions in αβ T cell biology were addressed by investigating a range of different genetically modified mouse models. In comparison, the γδ T cell field lacks behind on the availability of such models. Nevertheless, transgenic mouse models proved useful for the investigation of γδ T cell biology and their stepwise development in the thymus. In general, animal models and especially mouse models give access to a wide range of opportunities of modulating γδ T cells, which is unachievable in human beings. Because of their complex biology and specific tissue tropism, it is especially challenging to investigate γδ T cells in in vitro experiments since they might not reliably reflect their behavior and phenotype under physiologic conditions. This review aims to provide a comprehensive historical overview about how different transgenic mouse models contributed in regards of the understanding of γδ T cell biology, whereby a special focus is set on studies including the elusive role of the γδTCR. Furthermore, evolutionary and translational remarks are discussed under the aspect of future implications for the field. The ultimate full understanding of γδ T cells will pave the way for their usage as a powerful new tool in immunotherapy.

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A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence

Cited by 99 publications

References 60 publications

γδ T cells modulate humoral immunity against Plasmodium berghei infection

γδ T cells modulate humoral immunity against Plasmodium berghei infection

Peripheral γδ T Cells Regulate Neutrophil Expansion and Recruitment in Experimental Psoriatic Arthritis

Resolving the mystery—How TCR transgenic mouse models shed light on the elusive case of gamma delta T cells

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