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  1. Article ; Online: Mesenchymal stromal cells in hematopoietic cell transplantation.

    Burnham, Andre J / Daley-Bauer, Lisa P / Horwitz, Edwin M

    Blood advances

    2021  Volume 4, Issue 22, Page(s) 5877–5887

    Abstract: Mesenchymal stromal cells (MSCs) are widely recognized to possess potent immunomodulatory activity, as well as to stimulate repair and regeneration of diseased or damaged tissue. These fundamental properties suggest important applications in ... ...

    Abstract Mesenchymal stromal cells (MSCs) are widely recognized to possess potent immunomodulatory activity, as well as to stimulate repair and regeneration of diseased or damaged tissue. These fundamental properties suggest important applications in hematopoietic cell transplantation. Although the mechanisms of therapeutic activity in vivo are yet to be fully elucidated, MSCs seem to suppress lymphocytes by paracrine mechanisms, including secreted mediators and metabolic modulators. Most recently, host macrophage engulfment of apoptotic MSCs has emerged as an important contributor to the immune suppressive microenvironment. Although bone marrow-derived MSCs are the most commonly studied, the tissue source of MSCs may be a critical determinant of immunomodulatory function. The key application of MSC therapy in hematopoietic cell transplantation is to prevent or treat graft-versus-host disease (GVHD). The pathogenesis of GVHD reveals multiple potential targets. Moreover, the recently proposed concept of tissue tolerance suggests a new possible mechanism of MSC therapy for GVHD. Beyond GVHD, MSCs may facilitate hematopoietic stem cell engraftment, which could gain greater importance with increasing use of haploidentical transplantation. Despite many challenges and much doubt, commercial MSC products for pediatric steroid-refractory GVHD have been licensed in Japan, conditionally licensed in Canada and New Zealand, and have been recommended for approval by an FDA Advisory Committee in the United States. Here, we review key historical data in the context of the most salient recent findings to present the current state of MSCs as adjunct cell therapy in hematopoietic cell transplantation.
    MeSH term(s) Canada ; Child ; Graft vs Host Disease/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Japan ; Mesenchymal Stem Cells
    Language English
    Publishing date 2021-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2020002646
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Caspase-8-dependent control of NK- and T cell responses during cytomegalovirus infection.

    Feng, Yanjun / Daley-Bauer, Lisa P / Mocarski, Edward S

    Medical microbiology and immunology

    2019  Volume 208, Issue 3-4, Page(s) 555–571

    Abstract: Caspase-8 (CASP8) impacts antiviral immunity in expected as well as unexpected ways. Mice with combined deficiency in CASP8 and RIPK3 cannot support extrinsic apoptosis or RIPK3-dependent programmed necrosis, enabling studies of CASP8 function without ... ...

    Abstract Caspase-8 (CASP8) impacts antiviral immunity in expected as well as unexpected ways. Mice with combined deficiency in CASP8 and RIPK3 cannot support extrinsic apoptosis or RIPK3-dependent programmed necrosis, enabling studies of CASP8 function without complications of unleashed necroptosis. These extrinsic cell death pathways are naturally targeted by murine cytomegalovirus (MCMV)-encoded cell death suppressors, showing they are key to cell-autonomous host defense. Remarkably, Casp8
    MeSH term(s) Animals ; Caspase 8/metabolism ; Cytomegalovirus Infections/immunology ; Disease Models, Animal ; Killer Cells, Natural/immunology ; Mice ; Mice, Knockout ; Muromegalovirus/growth & development ; Muromegalovirus/immunology ; T-Lymphocytes/immunology
    Chemical Substances Casp8 protein, mouse (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-)
    Language English
    Publishing date 2019-05-16
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 120933-4
    ISSN 1432-1831 ; 0300-8584
    ISSN (online) 1432-1831
    ISSN 0300-8584
    DOI 10.1007/s00430-019-00616-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Viral Replication Assay in Bone Marrow-Derived Macrophages.

    Roback, Linda / Daley-Bauer, Lisa P

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1784, Page(s) 127–134

    Abstract: The selection of macrophages as a cell type for investigating virus-host interactions is based on cellular tropism of the virus during infection as well as contribution of these cells to pathogenesis in the host. In response to mouse cytomegalovirus ( ... ...

    Abstract The selection of macrophages as a cell type for investigating virus-host interactions is based on cellular tropism of the virus during infection as well as contribution of these cells to pathogenesis in the host. In response to mouse cytomegalovirus (MCMV) infection, bone marrow-resident monocytes that mobilize to infected tissues to differentiate into macrophages and dendritic cells are hijacked in order to facilitate viral persistence. These cells contribute significantly to MCMV biology and, thus, are actively recruited by the virus-encoded chemokine. In this chapter, we provide detailed methodologies employed in our laboratory to assess MCMV replication in bone marrow-derived macrophages.
    MeSH term(s) Animals ; Cell Differentiation/immunology ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/virology ; Dendritic Cells/immunology ; Dendritic Cells/virology ; Host-Parasite Interactions/immunology ; Macrophages/immunology ; Macrophages/virology ; Mice ; Molecular Biology/methods ; Monocytes/immunology ; Monocytes/virology ; Muromegalovirus/immunology ; Muromegalovirus/pathogenicity ; Virus Replication/genetics ; Virus Replication/immunology
    Language English
    Publishing date 2018-04-20
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7837-3_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Growing Murine Bone Marrow-Derived Macrophages.

    Assouvie, Anaïs / Daley-Bauer, Lisa P / Rousselet, Germain

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1784, Page(s) 29–33

    Abstract: Bone marrow-derived macrophages (BMDM) are primary macrophages obtained by in vitro differentiation of bone marrow cells in the presence of macrophage colony-stimulating factor (M-CSF or CSF1). They are easy to obtain in high yields, can be stored by ... ...

    Abstract Bone marrow-derived macrophages (BMDM) are primary macrophages obtained by in vitro differentiation of bone marrow cells in the presence of macrophage colony-stimulating factor (M-CSF or CSF1). They are easy to obtain in high yields, can be stored by freezing, and can be obtained from genetically modified mice strains. They are therefore widely used as prototypical macrophages for in vitro studies. In this chapter, we present the method for obtaining BMDMs and freezing them.
    MeSH term(s) Animals ; Bone Marrow/growth & development ; Bone Marrow Cells/cytology ; Cell Culture Techniques/methods ; Cell Differentiation/drug effects ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages/cytology ; Mice
    Chemical Substances Macrophage Colony-Stimulating Factor (81627-83-0)
    Language English
    Publishing date 2018-04-20
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7837-3_3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Caspase-8 restricts natural killer cell accumulation during MCMV Infection.

    Feng, Yanjun / Daley-Bauer, Lisa P / Roback, Linda / Potempa, Marc / Lanier, Lewis L / Mocarski, Edward S

    Medical microbiology and immunology

    2019  Volume 208, Issue 3-4, Page(s) 543–554

    Abstract: Natural killer (NK) cells provide important host defense against herpesvirus infections and influence subsequent T cell control of replication and maintenance of latency. NK cells exhibit phases of expansion, contraction and memory formation in response ... ...

    Abstract Natural killer (NK) cells provide important host defense against herpesvirus infections and influence subsequent T cell control of replication and maintenance of latency. NK cells exhibit phases of expansion, contraction and memory formation in response to the natural mouse pathogen murine cytomegalovirus (MCMV). Innate and adaptive immune responses are tightly regulated in mammals to avoid excess tissue damage while preventing acute and chronic viral disease and assuring resistance to reinfection. Caspase (CASP)8 is an autoactivating aspartate-specific cysteine protease that initiates extrinsic apoptosis and prevents receptor interacting protein (RIP) kinase (RIPK)1-RIPK3-driven necroptosis. CASP8 also promotes death-independent signal transduction. All of these activities make contributions to inflammation. Here, we demonstrate that CASP8 restricts NK cell expansion during MCMV infection but does not influence NK memory. Casp8
    MeSH term(s) Animals ; Caspase 8/metabolism ; Cytomegalovirus Infections/immunology ; Disease Models, Animal ; Killer Cells, Natural/immunology ; Mice ; Mice, Inbred C57BL ; Muromegalovirus/growth & development ; Muromegalovirus/immunology
    Chemical Substances Casp8 protein, mouse (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-)
    Language English
    Publishing date 2019-05-21
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 120933-4
    ISSN 1432-1831 ; 0300-8584
    ISSN (online) 1432-1831
    ISSN 0300-8584
    DOI 10.1007/s00430-019-00617-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Caspase-8 restricts antiviral CD8 T cell hyperaccumulation.

    Feng, Yanjun / Daley-Bauer, Lisa P / Roback, Linda / Guo, Hongyan / Koehler, Heather S / Potempa, Marc / Lanier, Lewis L / Mocarski, Edward S

    Proceedings of the National Academy of Sciences of the United States of America

    2019  Volume 116, Issue 30, Page(s) 15170–15177

    Abstract: The magnitude of CD8 T cell responses against viruses is checked by the balance of proliferation and death. Caspase-8 (CASP8) has the potential to influence response characteristics through initiation of apoptosis, suppression of necroptosis, and ... ...

    Abstract The magnitude of CD8 T cell responses against viruses is checked by the balance of proliferation and death. Caspase-8 (CASP8) has the potential to influence response characteristics through initiation of apoptosis, suppression of necroptosis, and modulation of cell death-independent signal transduction. Mice deficient in CASP8 and RIPK3 (
    MeSH term(s) Adoptive Transfer ; Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/virology ; Caspase 8/genetics ; Caspase 8/immunology ; Cell Proliferation ; Cytomegalovirus Infections/genetics ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/virology ; Female ; Gene Expression Regulation ; Herpes Simplex/genetics ; Herpes Simplex/immunology ; Herpes Simplex/virology ; Herpesvirus 1, Human/immunology ; Herpesvirus 1, Human/pathogenicity ; Immunologic Memory ; Lectins, C-Type/genetics ; Lectins, C-Type/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muromegalovirus/immunology ; Muromegalovirus/pathogenicity ; Receptor-Interacting Protein Serine-Threonine Kinases/deficiency ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics ; Receptor-Interacting Protein Serine-Threonine Kinases/immunology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology ; Signal Transduction ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/virology
    Chemical Substances Klrg1 protein, mouse ; Lectins, C-Type ; Receptors, Antigen, T-Cell ; Receptors, Immunologic ; Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Ripk3 protein, mouse (EC 2.7.11.1) ; Casp8 protein, mouse (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-)
    Language English
    Publishing date 2019-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1904319116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Remarkably Robust Antiviral Immune Response despite Combined Deficiency in Caspase-8 and RIPK3.

    Feng, Yanjun / Livingston-Rosanoff, Devon / Roback, Linda / Sundararajan, Aarthi / Speck, Samuel H / Mocarski, Edward S / Daley-Bauer, Lisa P

    Journal of immunology (Baltimore, Md. : 1950)

    2018  Volume 201, Issue 8, Page(s) 2244–2255

    Abstract: Caspase-8 (Casp8)-mediated signaling triggers extrinsic apoptosis while suppressing receptor-interacting protein kinase (RIPK) 3-dependent necroptosis. Although Casp8 is dispensable for the development of innate and adaptive immune compartments in mice, ... ...

    Abstract Caspase-8 (Casp8)-mediated signaling triggers extrinsic apoptosis while suppressing receptor-interacting protein kinase (RIPK) 3-dependent necroptosis. Although Casp8 is dispensable for the development of innate and adaptive immune compartments in mice, the importance of this proapoptotic protease in the orchestration of immune response to pathogens remains to be fully explored. In this study,
    MeSH term(s) Adaptive Immunity ; Animals ; Antigens, Viral/immunology ; Apoptosis ; Caspase 8/genetics ; Dendritic Cells/immunology ; Dendritic Cells/virology ; Herpesviridae Infections/immunology ; Humans ; Immunity, Innate ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Muromegalovirus/physiology ; Necrosis ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Signal Transduction
    Chemical Substances Antigens, Viral ; Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Ripk3 protein, mouse (EC 2.7.11.1) ; Caspase 8 (EC 3.4.22.-)
    Language English
    Publishing date 2018-09-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1800110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Viral immunity: Basic mechanisms and therapeutic applications-a Keystone Symposia report.

    Cable, Jennifer / Balachandran, Siddharth / Daley-Bauer, Lisa P / Rustagi, Arjun / Antony, Ferrin / Frere, Justin J / Strampe, Jamie / Kedzierska, Katherine / Cannon, Judy L / McGargill, Maureen A / Weiskopf, Daniela / Mettelman, Robert C / Niessl, Julia / Thomas, Paul G / Briney, Bryan / Valkenburg, Sophie A / Bloom, Jesse D / Bjorkman, Pamela J / Iketani, Sho /
    Rappazzo, C Garrett / Crooks, Chelsea M / Crofts, Kali F / Pöhlmann, Stefan / Krammer, Florian / Sant, Andrea J / Nabel, Gary J / Schultz-Cherry, Stacey

    Annals of the New York Academy of Sciences

    2023  Volume 1521, Issue 1, Page(s) 32–45

    Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses ... ...

    Abstract Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.
    MeSH term(s) Humans ; Pandemics ; Influenza, Human/epidemiology
    Language English
    Publishing date 2023-01-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.14960
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Mouse cytomegalovirus M36 and M45 death suppressors cooperate to prevent inflammation resulting from antiviral programmed cell death pathways.

    Daley-Bauer, Lisa P / Roback, Linda / Crosby, Lynsey N / McCormick, A Louise / Feng, Yanjun / Kaiser, William J / Mocarski, Edward S

    Proceedings of the National Academy of Sciences of the United States of America

    2017  Volume 114, Issue 13, Page(s) E2786–E2795

    Abstract: The complex interplay between caspase-8 and receptor-interacting protein (RIP) kinase RIP 3 (RIPK3) driving extrinsic apoptosis and necroptosis is not fully understood. Murine cytomegalovirus triggers both apoptosis and necroptosis in infected cells; ... ...

    Abstract The complex interplay between caspase-8 and receptor-interacting protein (RIP) kinase RIP 3 (RIPK3) driving extrinsic apoptosis and necroptosis is not fully understood. Murine cytomegalovirus triggers both apoptosis and necroptosis in infected cells; however, encoded inhibitors of caspase-8 activity (M36) and RIP3 signaling (M45) suppress these antiviral responses. Here, we report that this virus activates caspase-8 in macrophages to trigger apoptosis that gives rise to secondary necroptosis. Infection with double-mutant ΔM36/M45mutRHIM virus reveals a signaling pattern in which caspase-8 activates caspase-3 to drive apoptosis with subsequent RIP3-dependent activation of mixed lineage kinase domain-like (MLKL) leading to necroptosis. This combined cell death signaling is highly inflammatory, greater than either apoptosis induced by ΔM36 or necroptosis induced by M45mutRHIM virus. IL-6 production by macrophages is dramatically increased during double-mutant virus infection and correlates with faster antiviral responses in the host. Collaboratively, M36 and M45 target caspase-8 and RIP3 pathways together to suppress this proinflammatory cell death. This study reveals the effect of antiviral programmed cell death pathways on inflammation, shows that caspase-8 activation may go hand-in-hand with necroptosis in macrophages, and revises current understanding of independent and collaborative functions of M36 and M45 in blocking apoptotic and necroptotic cell death responses.
    MeSH term(s) Animals ; Apoptosis ; Caspase 8/genetics ; Caspase 8/immunology ; Herpesviridae Infections/immunology ; Herpesviridae Infections/physiopathology ; Herpesviridae Infections/veterinary ; Herpesviridae Infections/virology ; Host-Pathogen Interactions ; Mice ; Muromegalovirus/classification ; Muromegalovirus/genetics ; Muromegalovirus/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics ; Receptor-Interacting Protein Serine-Threonine Kinases/immunology ; Ribonucleotide Reductases/genetics ; Ribonucleotide Reductases/metabolism ; Rodent Diseases/genetics ; Rodent Diseases/immunology ; Rodent Diseases/physiopathology ; Rodent Diseases/virology ; Viral Proteins/genetics ; Viral Proteins/metabolism
    Chemical Substances M36 protein, mouse cytomegalovirus ; Viral Proteins ; Ribonucleotide Reductases (EC 1.17.4.-) ; m45 protein, Mouse cytomegalovirus 1 (EC 1.17.4.-) ; Receptor-Interacting Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Ripk3 protein, mouse (EC 2.7.11.1) ; Caspase 8 (EC 3.4.22.-)
    Language English
    Publishing date 2017--28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1616829114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Cytomegalovirus impairs antiviral CD8+ T cell immunity by recruiting inflammatory monocytes.

    Daley-Bauer, Lisa P / Wynn, Grace M / Mocarski, Edward S

    Immunity

    2012  Volume 37, Issue 1, Page(s) 122–133

    Abstract: Inflammatory monocytes are key early responders to infection that contribute to pathogen-host interactions in diverse ways. Here, we report that the murine cytomegalovirus-encoded CC chemokine, MCK2, enhanced CCR2-dependent recruitment of these cells to ... ...

    Abstract Inflammatory monocytes are key early responders to infection that contribute to pathogen-host interactions in diverse ways. Here, we report that the murine cytomegalovirus-encoded CC chemokine, MCK2, enhanced CCR2-dependent recruitment of these cells to modulate antiviral immunity, impairing virus-specific CD8(+) T cell expansion and differentiation into effector cytotoxic T lymphocytes, thus reducing the capacity to eliminate viral antigen-bearing cells and slowing viral clearance. Adoptive transfer of inflammatory monocytes into Ccr2(-/-)Ccl2(-/-) mice impaired virus antigen-specific clearance. Cytomegalovirus therefore enhances a natural CCR2-dependent immune regulatory network to modulate adaptive immunity via nitric oxide production, reminiscent of the monocytic subtype of myeloid-derived suppressor cells primarily implicated in cancer immunomodulation.
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Chemokine CCL2/genetics ; Chemokine CCL2/immunology ; Chemokine CCL2/metabolism ; Chemokines, CC/immunology ; Herpesviridae Infections/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes/immunology ; Muromegalovirus/immunology ; Nitric Oxide/biosynthesis ; Viral Proteins/immunology
    Chemical Substances Chemokine CCL2 ; Chemokines, CC ; MCK-2 protein, Mouse cytomegalovirus 1 ; Viral Proteins ; Nitric Oxide (31C4KY9ESH)
    Language English
    Publishing date 2012-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2012.04.014
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