Patterns of lymphokine secretion amongst mouse γδ T cell clones

Duhindan, N.; Farley, Adrian J.; Humphreys, Sian; Parker, Claire E; Rossiter, Beth; Brooks, Colin G.

doi:10.1002/eji.1830270717

Cited by 21 publications

(17 citation statements)

References 25 publications

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“…5D), thus suggesting that cell-tocell contact between the infected macrophages and TCR gd T cells, rather than secreted factors, is therefore required for the IL-17A-dependent induction of the adhesion molecules. In line with this hypothesis, the addition of mAb against IFN-g and TNF-a, two representative TCR gd T cell-derived cytokines (29), failed to suppress the induction of adhesion molecules in the coculture of the BCG-infected macrophages and WT TCRVg6 + gd T cells (Fig. 5E).…”

Section: Il-17a-producing Tcr Vg4 + or Vg6 + Gd T Cells Induce Granulsupporting

confidence: 61%

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Yoshida

Umemura

Yahagi

et al. 2010

The Journal of Immunology

355

261

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Granulomas play an essential role in the sequestration and killing of mycobacteria in the lung; however, the mechanisms of their development and maturation are still not clearly understood. IL-17A is involved in mature granuloma formation in the mycobacteria-infected lung. Therefore, IL-17A gene-knockout (KO) mice fail to develop mature granulomas in the Mycobacterium bovis bacille Calmette-Guérin (BCG)-infected lung. This study analyzed the mechanism of IL-17A–dependent mature granuloma formation in the mycobacteria-infected lung. The IL-17A KO mice showed a normal level of nascent granuloma formation on day 14 but failed to develop mature granulomas on day 28 after the BCG infection in the lung. The observation implies that IL-17A is required for the maturation of granuloma from the nascent to mature stage. TCR γδ T cells expressing TCR Vγ4 or Vγ6 were identified as the major IL-17A–producing cells that resided in the BCG-induced lung granuloma. The adoptive transfer of the IL-17A–producing TCR γδ T cells reconstituted granuloma formation in the IL-17A KO mice. The expression of ICAM-1 and LFA-1, which are adhesion molecules important in granuloma formation, decreased in the lung of the BCG-infected IL-17A KO mice, and their expression was induced on BCG-infected macrophages in coculture with IL-17A–producing TCR γδ T cells. Furthermore, IL-17A KO mice showed not only an impaired mature granuloma formation, but also an impaired protective response to virulent Mycobacterium tuberculosis. Therefore, IL-17A produced by TCR γδ T cells plays a critical role in the prevention of M. tuberculosis infection through the induction of mature granuloma formation.

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Section: Il-17a-producing Tcr Vg4 + or Vg6 + Gd T Cells Induce Granulsupporting

confidence: 61%

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Yoshida

Umemura

Yahagi

et al. 2010

The Journal of Immunology

355

261

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“…The contribution of ␥␦ T cells in the initiation of inflammatory response during influenza virus infection suggests a role for ␥␦ T cells in viral immunity (14,19). Furthermore, ␥␦ T cells appear to modulate host immune response in several pathologies by producing several type 1 and/or type 2 cytokines (20,21), including IFN-␥, IL-2, IL-4, and IL-10 (22, 23). However, under pathological conditions, ␥␦ T cells have not been described as a major lymphocyte population in the CNS.…”

Section: N Eurocysticercosis (Ncc)mentioning

confidence: 99%

γ/δ T Cell-Deficient Mice Exhibit Reduced Disease Severity and Decreased Inflammatory Response in the Brain in Murine Neurocysticercosis

Cardona

Teale

2002

The Journal of Immunology

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In a recently developed mouse model for neurocysticercosis, the immune response was characterized by a massive influx of γδ T cells and a type 1 pathway of cytokine expression. To understand the role of γδ T cells during this infection, the cellular and cytokine response was analyzed in mice that lack γδ T cells (TCRδ−/−). In TCRδ−/− mice, Mesocestoides corti metacestodes preferentially invaded the extraparenchymal areas of the brain. Furthermore, parasites were able to escape from the brain and establish a systemic infection with liver and peritoneal involvement. Immunopathological studies indicated that TCRδ−/− mice develop little inflammatory response and less neurological symptomatology. Significantly reduced numbers of T cells, macrophages, dendritic cells, and mast cells were present in the brain. The cytokine response in the brain of TCRδ−/− mice appears to be a mixed type1/type 2 response with low levels of IL-2, IL-4, IL-10, IL-12, IL-13, IL-15, and IFN-γ. To further investigate the immunological significance of this cell population, γδ T cells were adoptively transferred into intracranially infected TCRδ−/− mice. γδ T cells were specifically recruited into the CNS in response to this parasitic infection, and they were able to target the infected brain within 12 h after transfer. These results suggest that γδ T cells are key players in the immune response elicited during this CNS infection and direct a type 1 response in wild-type mice upon infection.

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“…In contrast, γδ T cells isolated from the spleen predominantly produce IFN-γ and TNF-α when activated by Con A [5]. Previously, two reports used γδ T cell-deficient mice to determine their role during bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

γδ T cells mitigate the organ injury and mortality of sepsis

Tschöp

Martignoni

Goetzman

et al. 2007

Journal of Leukocyte Biology

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Sepsis is a difficult condition to treat and is associated with a high mortality rate. Sepsis is known to cause a marked depletion of lymphocytes, although the function of different lymphocyte subsets in the response to sepsis is unclear. γδ T cells are found largely in epithelial-rich tissues, and previous studies of γδ T cells in models of sepsis have yielded divergent results. In the present study, we examined the function of γδ T cells during sepsis in mice using cecal ligation and puncture (CLP). Mice deficient in γδ T cells had decreased survival times and increased tissue damage after CLP compared with wild-type mice. Furthermore, bacterial load was increased in γδ T cell-deficient mice, yet antibiotic treatment did not change mortality. Additionally, we found that recruitment of neutrophils and myeloid suppressor cells to the site of infection was diminished in γδ T cell-deficient mice. Finally, we found that circulating levels of IFN-γ were increased, and systemic levels of IL-10 were decreased in γδ T cell-deficient mice after CLP compared with wild-type mice. γδ T celldeficient mice also had increased intestinal permeability after CLP compared with wild-type mice. Neutralization of IFN-γ abrogated the increase in intestinal permeability in γδ T cell-deficient mice. The intestines taken from γδ T cell-deficient mice had decreased myeloperoxidase yet had increased tissue damage as compared with wild-type mice. Collectively, our data suggest that γδ T cells modulate the response to sepsis and may be a potential therapeutic target.

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Patterns of lymphokine secretion amongst mouse γδ T cell clones

Cited by 21 publications

References 25 publications

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

γ/δ T Cell-Deficient Mice Exhibit Reduced Disease Severity and Decreased Inflammatory Response in the Brain in Murine Neurocysticercosis

γδ T cells mitigate the organ injury and mortality of sepsis

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