Immunological lessons learnt from patients transplanted with fully mismatched stem cells
Fully HLA-mismatched stem cells from human fetal livers were transplanted into 17 infants and two fetuses to treat severe combined immunodeficiency disease in 1976-2000. Donor cell engraftment and immunological reconstitution were obtained in 14/19 patients, three of whom have been extensively and r...
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| Veröffentlicht in: | Immunologic research 2007-01, Vol.38 (1-3), p.201-209 |
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| creator | Touraine, Jean-Louis Plotnicky, Hélène Roncarolo, Maria-Grazia Bacchetta, Rosa Gebuhrer, Lucette |
| description | Fully HLA-mismatched stem cells from human fetal livers were transplanted into 17 infants and two fetuses to treat severe combined immunodeficiency disease in 1976-2000. Donor cell engraftment and immunological reconstitution were obtained in 14/19 patients, three of whom have been extensively and repeatedly studied immunologically during prolonged follow-up. T-cells were derived totally from donor cells; B-cells and antigen-presenting cells (APC) remained mainly of host origin. Due to class I and II mismatches between T-cells and all other cells (APC, B-cells, virus-infected target cells), limitations in the defense against infections in vivo and in T-cell functions in vitro (helper and cytotoxic activities) were predicted; however, these did not occur. Anti-tetanus toxoid responses (including specific antibody production) developed despite HLA disparities between T-cells and B-cells or APC in the chimeric children. Similarly, cytotoxic T-cells (of donor HLA phenotype) recognized host Epstein-Barr virus-infected target cells. Recognition of antigenic peptide by T-cells under these conditions involved presentation by host allogeneic HLA molecules and not by self HLA antigens. Tolerance to donor antigens was acquired by clonal deletion; tolerance to host antigens existed despite the presence of many host-reactive T-cells and involved clonal anergy. |
| doi_str_mv | 10.1007/s12026-007-0002-6 |
| format | Article |
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Donor cell engraftment and immunological reconstitution were obtained in 14/19 patients, three of whom have been extensively and repeatedly studied immunologically during prolonged follow-up. T-cells were derived totally from donor cells; B-cells and antigen-presenting cells (APC) remained mainly of host origin. Due to class I and II mismatches between T-cells and all other cells (APC, B-cells, virus-infected target cells), limitations in the defense against infections in vivo and in T-cell functions in vitro (helper and cytotoxic activities) were predicted; however, these did not occur. Anti-tetanus toxoid responses (including specific antibody production) developed despite HLA disparities between T-cells and B-cells or APC in the chimeric children. Similarly, cytotoxic T-cells (of donor HLA phenotype) recognized host Epstein-Barr virus-infected target cells. Recognition of antigenic peptide by T-cells under these conditions involved presentation by host allogeneic HLA molecules and not by self HLA antigens. Tolerance to donor antigens was acquired by clonal deletion; tolerance to host antigens existed despite the presence of many host-reactive T-cells and involved clonal anergy.</description><identifier>ISSN: 0257-277X</identifier><identifier>EISSN: 1559-0755</identifier><identifier>DOI: 10.1007/s12026-007-0002-6</identifier><identifier>PMID: 17917026</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>Antigens ; Clonal Anergy ; Cytotoxicity, Immunologic ; Female ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells - immunology ; Histocompatibility Testing ; HLA Antigens - immunology ; Humans ; Immune system ; Infant ; Life Sciences ; Living Donors ; Male ; Peptides ; Severe Combined Immunodeficiency - surgery ; Stem cells ; T cell receptors ; T-Lymphocytes - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Transplantation Tolerance ; Transplants & implants ; Treatment Outcome</subject><ispartof>Immunologic research, 2007-01, Vol.38 (1-3), p.201-209</ispartof><rights>Humana Press Inc. 2007</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-fc2d5e9a40c37adb8513be1edc2cda71d27af989fbc849c58bbe3cdab44f72e43</citedby><cites>FETCH-LOGICAL-c391t-fc2d5e9a40c37adb8513be1edc2cda71d27af989fbc849c58bbe3cdab44f72e43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17917026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-02660488$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Touraine, Jean-Louis</creatorcontrib><creatorcontrib>Plotnicky, Hélène</creatorcontrib><creatorcontrib>Roncarolo, Maria-Grazia</creatorcontrib><creatorcontrib>Bacchetta, Rosa</creatorcontrib><creatorcontrib>Gebuhrer, Lucette</creatorcontrib><title>Immunological lessons learnt from patients transplanted with fully mismatched stem cells</title><title>Immunologic research</title><addtitle>Immunol Res</addtitle><description>Fully HLA-mismatched stem cells from human fetal livers were transplanted into 17 infants and two fetuses to treat severe combined immunodeficiency disease in 1976-2000. Donor cell engraftment and immunological reconstitution were obtained in 14/19 patients, three of whom have been extensively and repeatedly studied immunologically during prolonged follow-up. T-cells were derived totally from donor cells; B-cells and antigen-presenting cells (APC) remained mainly of host origin. Due to class I and II mismatches between T-cells and all other cells (APC, B-cells, virus-infected target cells), limitations in the defense against infections in vivo and in T-cell functions in vitro (helper and cytotoxic activities) were predicted; however, these did not occur. Anti-tetanus toxoid responses (including specific antibody production) developed despite HLA disparities between T-cells and B-cells or APC in the chimeric children. Similarly, cytotoxic T-cells (of donor HLA phenotype) recognized host Epstein-Barr virus-infected target cells. Recognition of antigenic peptide by T-cells under these conditions involved presentation by host allogeneic HLA molecules and not by self HLA antigens. Tolerance to donor antigens was acquired by clonal deletion; tolerance to host antigens existed despite the presence of many host-reactive T-cells and involved clonal anergy.</description><subject>Antigens</subject><subject>Clonal Anergy</subject><subject>Cytotoxicity, Immunologic</subject><subject>Female</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic Stem Cells - immunology</subject><subject>Histocompatibility Testing</subject><subject>HLA Antigens - immunology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infant</subject><subject>Life Sciences</subject><subject>Living Donors</subject><subject>Male</subject><subject>Peptides</subject><subject>Severe Combined Immunodeficiency - surgery</subject><subject>Stem cells</subject><subject>T cell receptors</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Transplantation Tolerance</subject><subject>Transplants & implants</subject><subject>Treatment Outcome</subject><issn>0257-277X</issn><issn>1559-0755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkc9LwzAUx4Mobk7_AC9SPAgeqkmaNM1xDH8MBl4UdgtpmrqOtJlJquy_N6VDwYuB8B4vn-_jvXwBuETwDkHI7j3CEOdpTOOFOM2PwBRRylPIKD0GU4gpSzFj6wk4834LIcoJyU7BBDGOWJROwXrZtn1njX1vlDSJ0d7bzscoXReS2tk22cnQ6C74JDjZ-Z2RXdBV8tWETVL3xuyTtvGtDGoTqz7oNlHaGH8OTmppvL44xBl4e3x4XTynq5en5WK-SlXGUUhrhSuquSRQZUxWZUFRVmqkK4VVJRmqMJM1L3hdqoJwRYuy1Fl8KQmpGdYkm4Hbse9GGrFzTSvdXljZiOf5Sgy1uGYOSVF8osjejOzO2Y9e-yDi6MO0stO29yIvMkIZp_-CKDLx62EEr_-AW9u7Li48MAWPZ-iGRkg5673T9c-cCIrBSDEaKYZ0MFLkUXN1aNyXra5-FQfnsm8Zapow</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Touraine, Jean-Louis</creator><creator>Plotnicky, Hélène</creator><creator>Roncarolo, Maria-Grazia</creator><creator>Bacchetta, Rosa</creator><creator>Gebuhrer, Lucette</creator><general>Springer Nature B.V</general><general>Humana Press</general><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>3V.</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7QL</scope><scope>7QO</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>1XC</scope></search><sort><creationdate>20070101</creationdate><title>Immunological lessons learnt from patients transplanted with fully mismatched stem cells</title><author>Touraine, Jean-Louis ; Plotnicky, Hélène ; Roncarolo, Maria-Grazia ; Bacchetta, Rosa ; Gebuhrer, Lucette</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-fc2d5e9a40c37adb8513be1edc2cda71d27af989fbc849c58bbe3cdab44f72e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Antigens</topic><topic>Clonal Anergy</topic><topic>Cytotoxicity, Immunologic</topic><topic>Female</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hematopoietic Stem Cells - immunology</topic><topic>Histocompatibility Testing</topic><topic>HLA Antigens - immunology</topic><topic>Humans</topic><topic>Immune system</topic><topic>Infant</topic><topic>Life Sciences</topic><topic>Living Donors</topic><topic>Male</topic><topic>Peptides</topic><topic>Severe Combined Immunodeficiency - surgery</topic><topic>Stem cells</topic><topic>T cell receptors</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Transplantation Tolerance</topic><topic>Transplants & implants</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Touraine, Jean-Louis</creatorcontrib><creatorcontrib>Plotnicky, Hélène</creatorcontrib><creatorcontrib>Roncarolo, Maria-Grazia</creatorcontrib><creatorcontrib>Bacchetta, Rosa</creatorcontrib><creatorcontrib>Gebuhrer, Lucette</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Immunologic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Touraine, Jean-Louis</au><au>Plotnicky, Hélène</au><au>Roncarolo, Maria-Grazia</au><au>Bacchetta, Rosa</au><au>Gebuhrer, Lucette</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunological lessons learnt from patients transplanted with fully mismatched stem cells</atitle><jtitle>Immunologic research</jtitle><addtitle>Immunol Res</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>38</volume><issue>1-3</issue><spage>201</spage><epage>209</epage><pages>201-209</pages><issn>0257-277X</issn><eissn>1559-0755</eissn><abstract>Fully HLA-mismatched stem cells from human fetal livers were transplanted into 17 infants and two fetuses to treat severe combined immunodeficiency disease in 1976-2000. Donor cell engraftment and immunological reconstitution were obtained in 14/19 patients, three of whom have been extensively and repeatedly studied immunologically during prolonged follow-up. T-cells were derived totally from donor cells; B-cells and antigen-presenting cells (APC) remained mainly of host origin. Due to class I and II mismatches between T-cells and all other cells (APC, B-cells, virus-infected target cells), limitations in the defense against infections in vivo and in T-cell functions in vitro (helper and cytotoxic activities) were predicted; however, these did not occur. Anti-tetanus toxoid responses (including specific antibody production) developed despite HLA disparities between T-cells and B-cells or APC in the chimeric children. Similarly, cytotoxic T-cells (of donor HLA phenotype) recognized host Epstein-Barr virus-infected target cells. Recognition of antigenic peptide by T-cells under these conditions involved presentation by host allogeneic HLA molecules and not by self HLA antigens. Tolerance to donor antigens was acquired by clonal deletion; tolerance to host antigens existed despite the presence of many host-reactive T-cells and involved clonal anergy.</abstract><cop>United States</cop><pub>Springer Nature B.V</pub><pmid>17917026</pmid><doi>10.1007/s12026-007-0002-6</doi><tpages>9</tpages></addata></record> |
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| subjects | Antigens Clonal Anergy Cytotoxicity, Immunologic Female Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells - immunology Histocompatibility Testing HLA Antigens - immunology Humans Immune system Infant Life Sciences Living Donors Male Peptides Severe Combined Immunodeficiency - surgery Stem cells T cell receptors T-Lymphocytes - immunology T-Lymphocytes, Cytotoxic - immunology Transplantation Tolerance Transplants & implants Treatment Outcome |
| title | Immunological lessons learnt from patients transplanted with fully mismatched stem cells |
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