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Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype
The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (...
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Published in: | PloS one 2012-08, Vol.7 (8), p.e44219-e44219 |
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description | The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD. |
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Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0044219</identifier><identifier>PMID: 22937164</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Antigens ; Biology ; Biomedical research ; Blood ; Bone marrow ; CD3 antigen ; CD45 antigen ; Cell culture ; Dermatology ; Disease ; Effector cells ; Ethics ; Female ; Graft vs Host Disease - immunology ; Graft vs Host Disease - pathology ; Graft-versus-host reaction ; Hematopoietic stem cells ; Homing ; Humans ; Immune response ; Immunodeficiency ; Immunological memory ; Immunotherapy ; In vivo methods and tests ; Infiltration ; Interleukin 2 ; Interleukin 2 receptors ; Interleukin Receptor Common gamma Subunit - genetics ; Kinetics ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - immunology ; Leukocytes, Mononuclear - transplantation ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Male ; Medical research ; Medicine ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Pathogenesis ; Peripheral blood mononuclear cells ; Phenotype ; Phenotypes ; Reaction kinetics ; Regulation ; Severe Combined Immunodeficiency - immunology ; Severe Combined Immunodeficiency - pathology ; Skin - immunology ; Skin - pathology ; Stem cell transplantation ; Stem cells ; T cell receptors ; T-Lymphocytes - immunology ; Transplantation ; Xenografts</subject><ispartof>PloS one, 2012-08, Vol.7 (8), p.e44219-e44219</ispartof><rights>Ali et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Ali et al 2012 Ali et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-ea7c5bf7a0a2c2b6626fe6769a3051133cac2f60133312251ee729c78323c4d63</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1326547277/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1326547277?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22937164$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stoddart, Cheryl A.</contributor><creatorcontrib>Ali, Niwa</creatorcontrib><creatorcontrib>Flutter, Barry</creatorcontrib><creatorcontrib>Sanchez Rodriguez, Robert</creatorcontrib><creatorcontrib>Sharif-Paghaleh, Ehsan</creatorcontrib><creatorcontrib>Barber, Linda D</creatorcontrib><creatorcontrib>Lombardi, Giovanna</creatorcontrib><creatorcontrib>Nestle, Frank O</creatorcontrib><title>Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antigens</subject><subject>Biology</subject><subject>Biomedical research</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>CD3 antigen</subject><subject>CD45 antigen</subject><subject>Cell culture</subject><subject>Dermatology</subject><subject>Disease</subject><subject>Effector cells</subject><subject>Ethics</subject><subject>Female</subject><subject>Graft vs Host Disease - immunology</subject><subject>Graft vs Host Disease - pathology</subject><subject>Graft-versus-host reaction</subject><subject>Hematopoietic stem cells</subject><subject>Homing</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunodeficiency</subject><subject>Immunological memory</subject><subject>Immunotherapy</subject><subject>In vivo methods and tests</subject><subject>Infiltration</subject><subject>Interleukin 2</subject><subject>Interleukin 2 receptors</subject><subject>Interleukin Receptor Common gamma Subunit - genetics</subject><subject>Kinetics</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Leukocytes, Mononuclear - transplantation</subject><subject>Lymph nodes</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, Knockout</subject><subject>Mice, SCID</subject><subject>Pathogenesis</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Reaction kinetics</subject><subject>Regulation</subject><subject>Severe Combined Immunodeficiency - immunology</subject><subject>Severe Combined Immunodeficiency - pathology</subject><subject>Skin - immunology</subject><subject>Skin - pathology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>T cell receptors</subject><subject>T-Lymphocytes - 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immunology</topic><topic>Graft vs Host Disease - pathology</topic><topic>Graft-versus-host reaction</topic><topic>Hematopoietic stem cells</topic><topic>Homing</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunodeficiency</topic><topic>Immunological memory</topic><topic>Immunotherapy</topic><topic>In vivo methods and tests</topic><topic>Infiltration</topic><topic>Interleukin 2</topic><topic>Interleukin 2 receptors</topic><topic>Interleukin Receptor Common gamma Subunit - genetics</topic><topic>Kinetics</topic><topic>Leukocytes (mononuclear)</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Leukocytes, Mononuclear - transplantation</topic><topic>Lymph nodes</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, Knockout</topic><topic>Mice, SCID</topic><topic>Pathogenesis</topic><topic>Peripheral blood mononuclear cells</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Reaction kinetics</topic><topic>Regulation</topic><topic>Severe Combined Immunodeficiency - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ali, Niwa</au><au>Flutter, Barry</au><au>Sanchez Rodriguez, Robert</au><au>Sharif-Paghaleh, Ehsan</au><au>Barber, Linda D</au><au>Lombardi, Giovanna</au><au>Nestle, Frank O</au><au>Stoddart, Cheryl A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-08-28</date><risdate>2012</risdate><volume>7</volume><issue>8</issue><spage>e44219</spage><epage>e44219</epage><pages>e44219-e44219</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22937164</pmid><doi>10.1371/journal.pone.0044219</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animal models Animals Antigens Biology Biomedical research Blood Bone marrow CD3 antigen CD45 antigen Cell culture Dermatology Disease Effector cells Ethics Female Graft vs Host Disease - immunology Graft vs Host Disease - pathology Graft-versus-host reaction Hematopoietic stem cells Homing Humans Immune response Immunodeficiency Immunological memory Immunotherapy In vivo methods and tests Infiltration Interleukin 2 Interleukin 2 receptors Interleukin Receptor Common gamma Subunit - genetics Kinetics Leukocytes (mononuclear) Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - transplantation Lymph nodes Lymphocytes Lymphocytes T Male Medical research Medicine Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Pathogenesis Peripheral blood mononuclear cells Phenotype Phenotypes Reaction kinetics Regulation Severe Combined Immunodeficiency - immunology Severe Combined Immunodeficiency - pathology Skin - immunology Skin - pathology Stem cell transplantation Stem cells T cell receptors T-Lymphocytes - immunology Transplantation Xenografts |
title | Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T22%3A45%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Xenogeneic%20graft-versus-host-disease%20in%20NOD-scid%20IL-2R%CE%B3null%20mice%20display%20a%20T-effector%20memory%20phenotype&rft.jtitle=PloS%20one&rft.au=Ali,%20Niwa&rft.date=2012-08-28&rft.volume=7&rft.issue=8&rft.spage=e44219&rft.epage=e44219&rft.pages=e44219-e44219&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0044219&rft_dat=%3Cproquest_plos_%3E2943632951%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c456t-ea7c5bf7a0a2c2b6626fe6769a3051133cac2f60133312251ee729c78323c4d63%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1326547277&rft_id=info:pmid/22937164&rfr_iscdi=true |