Mechanism of murine Vγ1+ γ δ T cell-mediated innate immune response againstListeria monocytogenes infection

Matsuzaki, Goro; Yamada, Hisakata; Kishihara, Kenji; Yoshikai, Yasunobu; Nomoto, Kikuo

doi:10.1002/1521-4141(200204)32:4<928::aid-immu928>3.0.co;2-i

Cited by 36 publications

(7 citation statements)

References 26 publications

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“…3g, h). Naïve splenic γδ T cells from non-immunized Bhlhe40 −/− mice were capable of responding to IL-1β, IL-23, and IL-12 41,43 , as demonstrated by their increased size and granularity, but failed to produce normal levels of GM-CSF in these cultures (Supplementary Fig. 6a, b).…”

Section: Resultsmentioning

confidence: 97%

Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation

et al. 2014

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TH1 and TH17 cells mediate neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Pathogenic TH cells in EAE must produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). TH cell pathogenicity in EAE is also regulated by cell-intrinsic production of the immunosuppressive cytokine interleukin 10 (IL-10). Here, we demonstrate that mice deficient for the basic helix-loop-helix (bHLH) transcription factor Bhlhe40 (Bhlhe40−/−) are resistant to the induction of EAE. Bhlhe40 is required in vivo in a T cell-intrinsic manner, where it positively regulates the production of GM-CSF and negatively regulates the production of IL-10. In vitro, GM-CSF secretion is selectively abrogated in polarized Bhlhe40−/− TH1 and TH17 cells, and these cells show increased production of IL-10. Blockade of IL-10 receptor in Bhlhe40−/− mice renders them susceptible to EAE. These findings identify Bhlhe40 as a critical regulator of autoreactive T cell pathogenicity.

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Section: Resultsmentioning

confidence: 97%

Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation

et al. 2014

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“…He et al reported that CD44-rich Vγ4 + γδT cells secreted more IFN-γ than Vγ1 + γδT cells, partly due to the high expression of eomesodermin ( 63 ). In contrast, Vγ1 + γδT cells were the major γδT subset that produced IFN-γ in response to L. monocytogenes infection ( 64 ). These conflicting results are likely due to different disease models and treatment methods ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Vγ4+γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A

et al. 2017

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The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleukin (IL)-17A production by humans or mice infected with influenza A (H1N1) pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1) pdm09 infection remained unknown. In this study, a mouse model of severe influenza A (H1N1) pdm09 infection was established. Our results show that, in the lungs of infected mice, the percentage of γδT cells, but not the percentages of CD4+Th and CD8+Tc cells, gradually increased and peaked at 3 days post-infection (dpi). Further analysis revealed that the Vγ4+γδT subset, but not the Vγ1+γδT subset, was significantly increased among the γδT cells. At 3 dpi, the virus induced significant increases in IL-17A in the bronchoalveolar lavage fluid (BALF) and serum. IL-17A was predominantly secreted by γδT cells (especially the Vγ4+γδT subset), but not CD4+Th and CD8+Tc cells at the early stage of infection, and IL-1β and/or IL-23 were sufficient to induce IL-17A production by γδT cells. In addition to secreting IL-17A, γδT cells secreted interferon (IFN)-γ and expressed both an activation-associated molecule, natural killer group 2, member D (NKG2D), and an apoptosis-associated molecule, FasL. Depletion of γδT cells or the Vγ4+γδT subset significantly rescued the virus-induced weight loss and improved the survival rate by decreasing IL-17A secretion and reducing immunopathological injury. This study demonstrated that, by secreting IL-17A, lung Vγ4+γδT cells, at least, in part mediated influenza A (H1N1) pdm09-induced immunopathological injury. This mechanism might serve as a promising new target for the prevention and treatment of ALI induced by influenza A (H1N1) pdm09.

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“…For example, Vγ1 + and Vγ4 + T cells are two major subpopulations of peripheral γδ T cells in mice. Splenic Vγ1-bearing T cells are important in the elimination of Listeria by their interferon (IFN)-γ– producing activity (Matsuzaki, et al ., 2002). In Coxsackievirus-infected mice, Vγ4 + T cells enhance CD4 + Th1 cell activation through IFN-γ and CD1-dependent mechanisms and promote the activation of autoimmune CD8 + T cells, which could ultimately lead to myocarditis (Huber, et al ., 2000).…”

Section: Introductionmentioning

confidence: 99%

Vγ4+T cells regulate host immune response to West Nile virus infection

Welte

Aronson

Gong

et al. 2011

FEMS Immunol Med Microbiol

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Vγ4+ cells, a subpopulation of peripheral γδ T cells, are involved in West Nile virus (WNV) pathogenesis, but the underlying mechanism is unclear. In this study, we found that WNV-infected Vγ4+ cell-depleted mice had lower viremia and a reduced inflammatory response in the brain. Vγ4+ cells produced interleukin (IL)-17 during WNV infection, but blocking IL-17 signaling did not affect host susceptibility to WNV encephalitis. We also noted that there was an enhanced magnitude of protective splenic Vγ1+ cell expansion in Vγ4+ cell-depleted mice compared to that in controls during WNV infection. Additionally, Vγ4+ cells of WNV-infected mice had a higher potential for producing transforming growth factor (TGF)-β. γδ T cells of WNV-infected Vγ4+ cell-depleted mice had a higher proliferation rate than those of WNV-infected controls upon ex vivo stimulation with anti-CD3, and this difference was diminished in the presence of TGF-β inhibitor. Finally, Vγ4+ cells of infected mice contributed directly and indirectly to the higher level of IL-10, which is known to play a negative role in immunity against WNV infection. In summary, Vγ4+ cells suppress Vγ1+ cell expansion via TGF-β and increase IL-10 level during WNV infection, which together may lead to higher viremia and enhanced brain inflammation.

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Mechanism of murine Vγ1+ γ δ T cell-mediated innate immune response againstListeria monocytogenes infection

Cited by 36 publications

References 26 publications

Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation

Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation

Vγ4+γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A

Vγ4+T cells regulate host immune response to West Nile virus infection

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