Phosphoantigen‐Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte‐Derived Macrophages Infected with Human and Avian Influenza Viruses

Qin, Gang; Mao, Huawei; Zheng, Jian; Sia, Sin Fun; Liu, Yinping; Chan, Ping-Lung; Lam, Kwok-Tai; Peiris, Jsm; Lau, Yu‐Lung; Tu, Wenwei

doi:10.1086/605413

Cited by 125 publications

(160 citation statements)

References 49 publications

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“…The following anti-human monoclonal antibodies (MAbs) were used in this study: anti-HLA-A2 (BB7.2), anti-CD45RO (UCHL1), anti-CCR7 (3D12), anti-CD62L (DREG-56), anti-IFN-␥ (25723.11), anti-TNF-␣ (6401.1111), antiperforin (G9), anti-granzyme B (GB11), and antiCD107a (H4A3) (all from BD Biosciences) and anti-CD3 (HIT3a), anti-CD8 (HIT8a), anti-CD19 (HIB19), anti-CCR5 (HEK/1/85a), and anti-CXCR3 (TG1/ CXCR3) (all from BioLegend). For intracellular staining, cells were fixed, permeabilized, and then labeled with the indicated antibody as we described before (36,44,59). In order to examine tetramer staining, cells were incubated with anti-CD3, anti-CD8, and HLA-A2/M1 [58][59][60][61][62][63][64][65][66] tetramer (Beckman Coulter, CA) for 30 min and then analyzed by flow cytometry.…”

Section: Cellsmentioning

confidence: 99%

“…After 1 h, the cells were washed and then cocultured with influenza virus bulk CTLs or M1 [58][59][60][61][62][63][64][65][66] -specific CTLs at the indicated E/T ratio for 4 to 6 h. After incubation, total cells were stained with anti-CD3 and EthD-2 as we described before (44). Dead target cells were identified as EthD-2-positive cells out of CD3-negative cells, and cell death was analyzed by flow cytometry.…”

Section: Cellsmentioning

confidence: 99%

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Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Mao

Zheng

et al. 2010

J Virol

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138

127

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While few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣). Using influenza A virus matrix protein 1 (M1 58-66 ) epitope-specific CTLs isolated from healthy HLA-A2 ؉ individuals, we further found that M1 58-66 epitope-specific CTLs efficiently killed both M1 58-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1 58-66 -specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1 58-66 epitope-specific CTLs in 20% (4/20) of HLA-A2 ؉ individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

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Section: Cellsmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Mao

Zheng

et al. 2010

J Virol

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138

127

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“…23 Briefly, CD40-B cells were labeled with 3,39-dioctadecyloxacarbocyanine perchlorate before beginning coculture. Cells were harvested and stained with propidium iodide for 15 min and analyzed by flow cytometry at the indicated times during coculture.…”

Section: Cell Death Assaymentioning

confidence: 99%

CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4+ regulatory T cells

et al. 2010

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CD4 1 regulatory T cells (Tregs) play an important role in maintaining immune tolerance by suppressing pathologic immune responses. The generation of large numbers of antigen-specific Tregs ex vivo is critical for the development of clinical immunotherapy based on the adoptive transfer of Tregs. Both CD40-activated B cells (CD40-B) and immature dendritic cells (imDCs) have been used as professional antigen-presenting cells (APCs) to generate antigen-specific Tregs. However, the efficiencies of CD40-B and imDCs to generate CD4 1 Tregs have not been compared directly and the mechanism driving the generation of these Tregs remains largely unknown. In this study, we found that CD40-B exhibited mature phenotypes and were more able to induce and expand CD4 high CD25 1 Tregs than imDCs. Moreover, Tregs induced by CD40-B had greater suppressive capacity than those induced by imDCs. The generation of CD4 high CD25 1 Tregs by CD40-B and imDCs is cell-cell contact dependent and partially relies on the expression of human leukocyte antigen (HLA)-DR and CD80/86. Differences in CD4 high CD25 1 Treg generation efficiency were largely explained by the production of endogenous IL-2 by CD40-B. Our results suggest that CD40-B is better able to generate large numbers of antigen-specific Tregs than imDCs. Additionally, using CD40-B to generate Tregs may accelerate the clinical use of Treg-based immunotherapy in the treatment of allograft rejection, graft versus host disease (GVHD) and autoimmune diseases.

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“…23,24 Similarly to the contribution of murine cd-T cells during recovery after influenza-caused pneumonia, 25 the beneficial effects of human Vc9Vd2 cd-T cells against influenza virus infection have also recently been confirmed by our laboratory. 22,26,27 Through the direct killing of virus-infected cells and the production of antiviral cytokines, Vc9Vd2 cd-T cells can control infection by different strains of the influenza virus, such as human seasonal H1N1, pandemic H1N1, and the avian H5N1 and H9N2 viruses. 22,26,27 Moreover, these antiviral activities can be significantly improved by phosphoantigen stimulation, which confers sufficient protection on humanized mice to prevent lethal influenza virus infection.…”

Section: Involvement Of Cd-t Cells In Infectious Diseasesmentioning

confidence: 99%

“…22,26,27 Through the direct killing of virus-infected cells and the production of antiviral cytokines, Vc9Vd2 cd-T cells can control infection by different strains of the influenza virus, such as human seasonal H1N1, pandemic H1N1, and the avian H5N1 and H9N2 viruses. 22,26,27 Moreover, these antiviral activities can be significantly improved by phosphoantigen stimulation, which confers sufficient protection on humanized mice to prevent lethal influenza virus infection. 28 In addition, another group has shown that cd-T cells can initiate efficient adaptive immunity through processing and presenting influenza virus-derived peptides to CD4 1 and CD8 1 T cells.…”

Section: Involvement Of Cd-t Cells In Infectious Diseasesmentioning

confidence: 99%

γδ-T cells: an unpolished sword in human anti-infection immunity

et al. 2012

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cd-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of cd-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis. cd-T cells have both 'innate' and 'adaptive' characteristics in the immune response, and their anti-infection activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in cd-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different cd-T cell subpopulations under specific conditions, cd-T cell-based therapy has great potential for the treatment of infectious diseases.

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Phosphoantigen‐Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte‐Derived Macrophages Infected with Human and Avian Influenza Viruses

Abstract: Our findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza-the use of phosphoantigens to activate gammadelta T cells against influenza virus infections.

Cited by 125 publications

References 49 publications

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4+ regulatory T cells

γδ-T cells: an unpolished sword in human anti-infection immunity

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