Partial Depletion of Natural CD4+CD25+ Regulatory T Cells with Anti-CD25 Antibody Does Not Alter the Course of Acute Influenza A Virus Infection

Betts, Richard J.; Ho, Adrian W. S.; Kemeny, David M.

doi:10.1371/journal.pone.0027849

Cited by 31 publications

(31 citation statements)

References 29 publications

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“…Anti-CD25 Ab decreased the frequency of CD25 hi CD4+ T cells but not that of CD25 lo CD4+ T cells. As previously reported (Betts, Ho et al, 2011), we also found that treatment with anti-CD25 Ab decreased the number of Measurements of serum levels of osteocalcin, a marker for bone formation revealed that iPTH increased bone formation in mice treated with Irr. Ab but not in those treated with anti-CD25 Ab ( figure 3O).…”

Section: Cd25supporting

confidence: 89%

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

D’Amelio

Tyagi

et al. 2017

EMBO Reports

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Teriparatide is a bone anabolic treatment for osteoporosis, modeled in animals by intermittent PTH (iPTH) administration. iPTH-induced bone anabolism involves CD8+ T cell production of the osteogenic Wnt ligand Wnt10b, induced via yet unknown mechanisms. Here we show that Teriparatide and iPTH cause a ~2-3-fold increase in the number of regulatory T cells (Tregs) in humans and mice. Attesting in vivo relevance, blockade of the Treg increase in mice prevents iPTH-induced CD8+ T cell Wnt10b production and bone anabolism. Mechanistically, Treg action on CD8+ T cells promotes binding of NFAT1/2 and SMAD3 complexes to a NFAT/SMADactivated Wnt10b promoter region that stimualtes Wnt10b gene expression in CD8+ T cells.

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Section: Cd25supporting

confidence: 89%

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

D’Amelio

Tyagi

et al. 2017

EMBO Reports

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“…Regardless, studies have found that a systemic injection of the anti-CD25 antibody neutralizes the suppressive effects of Tregs (3,14), but may also inadvertently deplete activated T cells (41). We found that depleting Tregs using the anti-CD25 antibody significantly enhanced T-cell activation (Fig.…”

Section: Ifncmentioning

confidence: 66%

Regulatory T Cells Are Critical for Clearing Influenza A Virus in Neonatal Mice

et al. 2015

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We previously reported that neonatal mice infected with influenza A virus (IAV) develop interstitial pneumonia characterized by reduced lung cytokine and chemokine responses. The failure of T cells to infiltrate the airways of neonates correlated with delayed clearance of sublethal IAV infections compared to adults. We hypothesized that negative regulators in the neonatal lungs such as cytokines or T regulatory (Treg) cells are responsible for these differences. Neonates either deficient in interleukin-10 (IL-10) or with T cells unresponsive to transforming growth factor-b signaling due to absence of SMAD family member 4 (Smad4) had similar IAV clearance kinetics to wild-type pups and no difference in T-cell responses. In contrast, functional depletion of Treg cells with anti-CD25 monoclonal antibody resulted in increased proportions of activated CD4 + T cells in the lungs, but failure to clear IAV. Similarly, scurfy pups (mutation in forkhead box P3 [Foxp3] rendering them deficient in Treg cells) had increased proportions of activated T cells in the lungs compared to littermate controls. Scurfy pups also had increased proportions of IL-13-producing CD4 + T cells. Interestingly, like anti-CD25-treated pups, scurfy pups had significantly elevated viral loads compared to controls. Based on these data, we conclude that Tregs are critical for clearance of IAV in neonatal mice.

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“…Three days prior to LCMV infection, IAV-immune mice received a single dose of 100 g of PC61 (anti-CD25) i.p. by following a well-established protocol for removal of Treg cell activity in vivo (16,33,37,38) (see Fig. 3a).…”

Section: Methodsmentioning

confidence: 99%

“…CD25), a well-established conventional technique, was used to remove Treg cell activity (Fig. 3a) (16,32,33,37,38). LCMV infection i.n.…”

Section: Enhanced Levels Of Treg Cells In Iav-immune Micementioning

confidence: 99%

PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection

Kraft

Wlodarczyk

Kenney

et al. 2013

J Virol

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Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV)infection During a lifetime the immune system is shaped by a history of infections. Prior infections with one pathogen may influence the severity of disease outcome to a subsequent infection with an unrelated pathogen, a phenomenon known as heterologous immunity (1). Enhanced immunopathology, which can be mediated by the activation of cross-reactive memory T cells, is one of the harmful consequences of heterologous immunity. For instance, it has been proposed during human infections that cross-reactive IAV-specific memory CD8 ϩ T cells can contribute to the induction of severe fulminant hepatitis during hepatitis C virus (HCV) infection and induction of acute infectious mononucleosis during Epstein-Barr virus (EBV) infection (2-4).Lung pathology is a common manifestation of respiratory infections and can vary greatly in severity in different individuals infected with the same pathogen. To investigate the role of altered immunopathology during heterologous immunity in a controlled experimental setting, we utilized a mouse model of IAV-immune mice infected with lymphocytic choriomeningitis virus (LCMV) (5). We initially chose these two viruses because they are phylogenetically unrelated and because they are naturally spread through infection of the respiratory mucosa and induce significant inflammation in the lung (6-11). Influenza virus is an extremely common respiratory pathogen in humans, and LCMV, which induces a flu-like illness in humans, is also a relatively common pathogen, with 5 to 14% of the general population being serologically positive (12). These IAV-immune mice infected with LCMV could develop acute lung injury similar to that seen in individuals that died during the H1N1 IAV pandemic in 1918, with enhanced bronchus-associated lymphoid tissue (BALT), mononuclear pneumonia, necrotizing bronchiolitis, vasculitis, and bronchiolization (13, 14) The severity of lung pathology varied among genetically identical mice from mild pneumonitis to severe mononuclear pneumonia, necrotizing bronchiolitis, and bronchiolization, an abnormal alveolar epithelial repair process considered premalignant and associated with idiopathic pulmonary fibrosis in humans. Although counterintuitive, severity of pathology did not directly correlate with LCMV titers. Instead, increased pathology was dependent on cross-reactive IAV-specific memory CD8 ϩ T cells (15). Disease severity was directly correlated with and could be predicted by the frequency of two IAV epitope-specific CD8 ϩ T-cell populations, PB1 703 and PA 224 , which are crossreactive with LCMV-GP 34 and -GP 276 , respectively. Eradication or functional ablation of these pathogenic populations of IAV-specific memory T cells using mutant viral strains, peptide-based tolerization strategies, or short-term anti-gamma interferon (IFN-␥) treatment prevented this pathology.Here, we continue to investigate this mouse model to determine if there are ot...

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Partial Depletion of Natural CD4+CD25+ Regulatory T Cells with Anti-CD25 Antibody Does Not Alter the Course of Acute Influenza A Virus Infection

Cited by 31 publications

References 29 publications

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH ‐induced bone anabolism in mice

Regulatory T Cells Are Critical for Clearing Influenza A Virus in Neonatal Mice

PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection

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