Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34+ cells
The NOD-LtSZ scid/scid (NOD/SCID) repopulation assay is the criterion for the study of self-renewal and multilineage differentiation of human hematopoietic stem cells. An important shortcoming of this model is the reported absence of T-cell development. We studied this aspect of the model and invest...
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| Veröffentlicht in: | Blood 2002-03, Vol.99 (5), p.1620-1626 |
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| creator | Kerre, Tessa C.C. De Smet, Greet De Smedt, Magda Zippelius, Alfred Pittet, Mikaël J. Langerak, Anton W. De Bosscher, José Offner, Fritz Vandekerckhove, Bart Plum, Jean |
| description | The NOD-LtSZ scid/scid (NOD/SCID) repopulation assay is the criterion for the study of self-renewal and multilineage differentiation of human hematopoietic stem cells. An important shortcoming of this model is the reported absence of T-cell development. We studied this aspect of the model and investigated how it could be optimized to support T-cell development. Occasionally, low-grade thymic engraftment was observed in NOD/SCID mice or Rag2−/−γc−/− mice. In contrast, the treatment of NOD/SCID mice with a monoclonal antibody against the murine interleukin-2Rβ, (IL-2Rβ) known to decrease natural killer cell activity, resulted in human thymopoiesis in up to 60% of the mice. T-cell development was phenotypically normal and resulted in polyclonal, mature, and functional CD1−TCRαβ+ CD4+ or CD8+single-positive T cells. In mice with ongoing thymopoiesis, peripheral T cells were observed. TREC analysis showed that T cells with a naive phenotype (CD45RA+) emerged from the thymus. In approximately half of these mice, the peripheral T cells included a pauciclonal outgrowth of CD45RO+ cells. These data suggest that all elements of a functional immune system were present in these animals. |
| doi_str_mv | 10.1182/blood.V99.5.1620 |
| format | Article |
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An important shortcoming of this model is the reported absence of T-cell development. We studied this aspect of the model and investigated how it could be optimized to support T-cell development. Occasionally, low-grade thymic engraftment was observed in NOD/SCID mice or Rag2−/−γc−/− mice. In contrast, the treatment of NOD/SCID mice with a monoclonal antibody against the murine interleukin-2Rβ, (IL-2Rβ) known to decrease natural killer cell activity, resulted in human thymopoiesis in up to 60% of the mice. T-cell development was phenotypically normal and resulted in polyclonal, mature, and functional CD1−TCRαβ+ CD4+ or CD8+single-positive T cells. In mice with ongoing thymopoiesis, peripheral T cells were observed. TREC analysis showed that T cells with a naive phenotype (CD45RA+) emerged from the thymus. In approximately half of these mice, the peripheral T cells included a pauciclonal outgrowth of CD45RO+ cells. These data suggest that all elements of a functional immune system were present in these animals.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V99.5.1620</identifier><identifier>PMID: 11861276</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - pharmacology ; Antigens, CD34 ; Biological and medical sciences ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Cell Differentiation ; Fetal Blood - cytology ; Graft Survival - drug effects ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells - cytology ; Humans ; Immunophenotyping ; Leukopoiesis - drug effects ; Medical sciences ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Models, Animal ; Receptors, Interleukin-2 - immunology ; T-Lymphocyte Subsets - cytology ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes - cytology ; T-Lymphocytes - immunology ; Thymus Gland - cytology ; Transfusions. Complications. Transfusion reactions. 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An important shortcoming of this model is the reported absence of T-cell development. We studied this aspect of the model and investigated how it could be optimized to support T-cell development. Occasionally, low-grade thymic engraftment was observed in NOD/SCID mice or Rag2−/−γc−/− mice. In contrast, the treatment of NOD/SCID mice with a monoclonal antibody against the murine interleukin-2Rβ, (IL-2Rβ) known to decrease natural killer cell activity, resulted in human thymopoiesis in up to 60% of the mice. T-cell development was phenotypically normal and resulted in polyclonal, mature, and functional CD1−TCRαβ+ CD4+ or CD8+single-positive T cells. In mice with ongoing thymopoiesis, peripheral T cells were observed. TREC analysis showed that T cells with a naive phenotype (CD45RA+) emerged from the thymus. In approximately half of these mice, the peripheral T cells included a pauciclonal outgrowth of CD45RO+ cells. These data suggest that all elements of a functional immune system were present in these animals.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antigens, CD34</subject><subject>Biological and medical sciences</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>Cell Differentiation</subject><subject>Fetal Blood - cytology</subject><subject>Graft Survival - drug effects</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Leukopoiesis - drug effects</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Models, Animal</subject><subject>Receptors, Interleukin-2 - immunology</subject><subject>T-Lymphocyte Subsets - cytology</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - immunology</subject><subject>Thymus Gland - cytology</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1vFDEQhi0EIkdCT4XcQBPtxfba-0EX3QWIFJEigdby2mPFyLtebG-k-wn8a3wfUiqqkUbPO3rnQegDJWtKO3Y1-BDM-lffr8WaNoy8QisqWFcRwshrtCKENBXvW3qG3qX0mxDKaybeorMSbihrmxX6e23UnMHgH_fbq4fN7RaPwYDHaZnnEHPCBp7Bh3mEKeNg8fwEU8i72Wnl_Q6ryWC7TDq7MB0Wo8pLBPyINXifsI1hxE_LqCa8jIPz-xjWIRp8qI4325pfHtkL9MYqn-D9aZ6jn19vHjffq7v7b7eb67tK80bkitNBMCY4hbaHoddgDIe-bmqubaeNsI3WljWWCKONslq1fQ9ECDPURnSdqM_R5-PdOYY_C6QsR5f2DdQEYUmypbzta0YLSI6gjiGlCFbO0Y0q7iQlcq9fHn6QRb8Ucq-_RD6ebi_DCOYlcPJdgE8nQKWiwkY1aZdeuFqQllBWuC9HDoqJZwdRJu1gKt-6CDpLE9z_W_wDpeSlCg</recordid><startdate>20020301</startdate><enddate>20020301</enddate><creator>Kerre, Tessa C.C.</creator><creator>De Smet, Greet</creator><creator>De Smedt, Magda</creator><creator>Zippelius, Alfred</creator><creator>Pittet, Mikaël J.</creator><creator>Langerak, Anton W.</creator><creator>De Bosscher, José</creator><creator>Offner, Fritz</creator><creator>Vandekerckhove, Bart</creator><creator>Plum, Jean</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20020301</creationdate><title>Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34+ cells</title><author>Kerre, Tessa C.C. ; De Smet, Greet ; De Smedt, Magda ; Zippelius, Alfred ; Pittet, Mikaël J. ; Langerak, Anton W. ; De Bosscher, José ; Offner, Fritz ; Vandekerckhove, Bart ; Plum, Jean</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-41b522541e79eb9cedd4e93634cf8cd5f6ccf26f05dcdafca799e055db3d58853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antigens, CD34</topic><topic>Biological and medical sciences</topic><topic>Bone marrow, stem cells transplantation. Graft versus host reaction</topic><topic>Cell Differentiation</topic><topic>Fetal Blood - cytology</topic><topic>Graft Survival - drug effects</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Leukopoiesis - drug effects</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Models, Animal</topic><topic>Receptors, Interleukin-2 - immunology</topic><topic>T-Lymphocyte Subsets - cytology</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - immunology</topic><topic>Thymus Gland - cytology</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kerre, Tessa C.C.</creatorcontrib><creatorcontrib>De Smet, Greet</creatorcontrib><creatorcontrib>De Smedt, Magda</creatorcontrib><creatorcontrib>Zippelius, Alfred</creatorcontrib><creatorcontrib>Pittet, Mikaël J.</creatorcontrib><creatorcontrib>Langerak, Anton W.</creatorcontrib><creatorcontrib>De Bosscher, José</creatorcontrib><creatorcontrib>Offner, Fritz</creatorcontrib><creatorcontrib>Vandekerckhove, Bart</creatorcontrib><creatorcontrib>Plum, Jean</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kerre, Tessa C.C.</au><au>De Smet, Greet</au><au>De Smedt, Magda</au><au>Zippelius, Alfred</au><au>Pittet, Mikaël J.</au><au>Langerak, Anton W.</au><au>De Bosscher, José</au><au>Offner, Fritz</au><au>Vandekerckhove, Bart</au><au>Plum, Jean</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34+ cells</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2002-03-01</date><risdate>2002</risdate><volume>99</volume><issue>5</issue><spage>1620</spage><epage>1626</epage><pages>1620-1626</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>The NOD-LtSZ scid/scid (NOD/SCID) repopulation assay is the criterion for the study of self-renewal and multilineage differentiation of human hematopoietic stem cells. An important shortcoming of this model is the reported absence of T-cell development. We studied this aspect of the model and investigated how it could be optimized to support T-cell development. Occasionally, low-grade thymic engraftment was observed in NOD/SCID mice or Rag2−/−γc−/− mice. In contrast, the treatment of NOD/SCID mice with a monoclonal antibody against the murine interleukin-2Rβ, (IL-2Rβ) known to decrease natural killer cell activity, resulted in human thymopoiesis in up to 60% of the mice. T-cell development was phenotypically normal and resulted in polyclonal, mature, and functional CD1−TCRαβ+ CD4+ or CD8+single-positive T cells. In mice with ongoing thymopoiesis, peripheral T cells were observed. TREC analysis showed that T cells with a naive phenotype (CD45RA+) emerged from the thymus. In approximately half of these mice, the peripheral T cells included a pauciclonal outgrowth of CD45RO+ cells. These data suggest that all elements of a functional immune system were present in these animals.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>11861276</pmid><doi>10.1182/blood.V99.5.1620</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - pharmacology Antigens, CD34 Biological and medical sciences Bone marrow, stem cells transplantation. Graft versus host reaction Cell Differentiation Fetal Blood - cytology Graft Survival - drug effects Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells - cytology Humans Immunophenotyping Leukopoiesis - drug effects Medical sciences Mice Mice, Inbred NOD Mice, SCID Models, Animal Receptors, Interleukin-2 - immunology T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - immunology T-Lymphocytes - cytology T-Lymphocytes - immunology Thymus Gland - cytology Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
| title | Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34+ cells |
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