Decreased CD4+CD29+ (Memory T) Cells in Patients with Chronic Granulomatous Disease

Hasui, Masafumi; Hattori, Kousuke; Taniuchi, Shoichiro; Kohdera, Urara; Nishikawa, Atushi; Kinoshita, Y; Kobayashi, Yohnosuke

doi:10.1093/infdis/167.4.983

Cited by 17 publications

(7 citation statements)

References 7 publications

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“…Additionally, decreased STAT5 activation may play a role in defects in survival in NOX2‐deficient T cells. There is an association of CGD with decreased memory T cells and B cells and, in vitro, oxidase‐deficient T cells demonstrate decreased survival that could only be partially rescued by IL‐7 . Taken together, these observations and the results of this report suggest the importance of NADPH oxidase‐mediated activation of STAT5 in T cells.…”

Section: Discussionsupporting

confidence: 68%

Decreased STAT5 phosphorylation and GATA‐3 expression in NOX2‐deficient T cells: Role in T helper development

et al. 2012

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Summary Absence of phagocyte NADPH oxidase (NOX2) activity causes chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent bacterial infections. In contrast to this innate immune deficit, CGD patients and animal models display predisposition to autoimmune disease and enhanced response to H. pylori and influenza infection. These data imply an altered, perhaps augmented, adaptive immune response in CGD. Previous data demonstrated functional NOX2 expression in T cells, and the goal was to determine if NOX2-deficient T cells are inherently altered in their responses. Activation of purified naive CD4+ T cells from NOX2-deficient mice led to augmented IFN-γ and diminished IL-4 production and an increased ratio of expression of the TH1-specific transcription factor T-bet versus the TH2-specfic transcription factor GATA-3, consistent with a TH1 skewing of naïve T cells. Selective inhibition of TCR-induced STAT5 phosphorylation was identified as a potential mechanism for skewed T helper differentiation. Exposure to anti-oxidants inhibited, while pro-oxidants augmented TH2 cytokine secretion and STAT5 phosphorylation, supporting the redox dependence of these signaling changes. These data suggest that TCR-induced ROS generation from NOX2 activation can regulate the adaptive immune response in a T cell inherent fashion, and propose a possible role for redox signaling in T helper differentiation.

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Section: Discussionsupporting

confidence: 68%

Decreased STAT5 phosphorylation and GATA‐3 expression in NOX2‐deficient T cells: Role in T helper development

et al. 2012

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“…Oxidants have important signaling roles in the activation and apoptosis of macrophages [1], the maturation of dendritic cells [2], and the proliferation of T cells [3]. Chronic granulomatous disease (CGD), a genetic disease in which the phagocyte oxidase fails to assemble and produce superoxide, causes defects in signaling cascades that impair phagocyte activation [45], antigen presentation [46], and the development of memory lymphocytes [47]. By analogy, M. tuberculosis secretion of SodA, an enzyme that inactivates superoxide, may induce a similar albeit localized deficiency of superoxide that inhibits the development of adaptive immunity, resulting in chronic infection rather than eradication of the pathogen.…”

Section: Discussionmentioning

confidence: 99%

Reducing the Activity and Secretion of Microbial Antioxidants Enhances the Immunogenicity of BCG

et al. 2009

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BackgroundIn early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production.Methodology/Principal FindingsTo determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli.Conclusions/SignificanceWe conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

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“…Varicella zoster virus infections in CGD show an unusual course.z Polymorphonuclear leukocytes from children with CGD are incapable of generating H 2 0 2 after stimulation with PMA or opsonized Recently, an abnormality of the memory T cell population in CGD has been reported. 20 We speculate that both the incapabil-ity of generating H 2 0 2 by PMN and the abnormality of memory Tcells might be related to unusual VZV infections in CGD.…”

Section: Discussionmentioning

confidence: 84%

Effect of varicella zoster virus antigen‐antibody complexes on hydrogen peroxide generation by human polymorphonuclear leukocytes

Fujiwara

Ihara

Yamawaki

et al. 1994

Pediatrics International

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Hydrogen peroxide (H2O2) generation by human polymorphonuclear leukocytes (PMN) incubated with varicella zoster virus (VZV) antigen was studied by cytofluorography. Hydrogen peroxide generation was detected in the presence of VZV‐seropositive sera. When seropositive sera were heat‐inactivated, H2O2 generation was reduced. When PMN were pre‐incubated with Leu‐1 1b, a monoclonal antibody to the Fc receptor on PMN, H2O2 generation was also reduced. These results suggest that VZV antigen‐antibody‐complement complexes induce H2O2 generation by PMN after these complexes attach to Fc receptors on PMN.

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Decreased CD4+CD29+ (Memory T) Cells in Patients with Chronic Granulomatous Disease

Cited by 17 publications

References 7 publications

Decreased STAT5 phosphorylation and GATA‐3 expression in NOX2‐deficient T cells: Role in T helper development

Decreased STAT5 phosphorylation and GATA‐3 expression in NOX2‐deficient T cells: Role in T helper development

Reducing the Activity and Secretion of Microbial Antioxidants Enhances the Immunogenicity of BCG

Effect of varicella zoster virus antigen‐antibody complexes on hydrogen peroxide generation by human polymorphonuclear leukocytes

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