Requirements for developing mixed-chimerism in nonmyeloablative total-lymphoid irradiated mice: Role of IL-4 and immunoredirection
Adult mice treated with total-lymphoid irradiation (TLI) followed by hematopoietic cell transfer develop stable mixed-chimerism. The purpose of the study is to examine the requirements for the development of mixed-chimerism and characterize the immune responses associated with mixed-chimerism. T-cel...
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Veröffentlicht in: | Transplantation 2002-10, Vol.74 (7), p.1021-1029 |
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description | Adult mice treated with total-lymphoid irradiation (TLI) followed by hematopoietic cell transfer develop stable mixed-chimerism. The purpose of the study is to examine the requirements for the development of mixed-chimerism and characterize the immune responses associated with mixed-chimerism.
T-cell number and function were examined in spleens of TLI-treated mice at various times after the completion of TLI by fluorescence-activated cell sorter (FACS) analysis and enzyme-linked immunosorbent assay (ELISA). TLI-treated BALB/c mice were injected with CAF(1) spleen cells between 2 and 28 days after completing TLI, with or without concurrent anti-IL-4. The extent of mixed-chimerism was determined using multiparameter FACS analysis. Enzyme-linked immunosorbent spot (ELISPOT) assays were used to measure anti-donor CD4+ and CD8+ immune responses.
TLI treatment results in transient lymphopenia, sparing CD4 cells relative to CD8 cells, followed by gradual, partial recovery over 28 days. Day 2 post-TLI T cells produce more interleukin (IL)-4, but less IL-2, interferon (IFN)-gamma and IL-10, while day 28 post-TLI T cells produce more IFN-gamma relative to IL-4. More than 70% of mice develop mixed-chimerism when injected with CAF(1) cells at 2 days post-TLI, while none become chimeric if injected at 28 days post-TLI. Mixed-chimeric mice contain more anti-donor Th2 CD4 cells and less anti-donor TC1 CD8 cells compared with nonchimeric mice and nonirradiated controls. Treatment with anti-IL-4 inhibits the development of mixed-chimerism ( |
doi_str_mv | 10.1097/00007890-200210150-00022 |
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T-cell number and function were examined in spleens of TLI-treated mice at various times after the completion of TLI by fluorescence-activated cell sorter (FACS) analysis and enzyme-linked immunosorbent assay (ELISA). TLI-treated BALB/c mice were injected with CAF(1) spleen cells between 2 and 28 days after completing TLI, with or without concurrent anti-IL-4. The extent of mixed-chimerism was determined using multiparameter FACS analysis. Enzyme-linked immunosorbent spot (ELISPOT) assays were used to measure anti-donor CD4+ and CD8+ immune responses.
TLI treatment results in transient lymphopenia, sparing CD4 cells relative to CD8 cells, followed by gradual, partial recovery over 28 days. Day 2 post-TLI T cells produce more interleukin (IL)-4, but less IL-2, interferon (IFN)-gamma and IL-10, while day 28 post-TLI T cells produce more IFN-gamma relative to IL-4. More than 70% of mice develop mixed-chimerism when injected with CAF(1) cells at 2 days post-TLI, while none become chimeric if injected at 28 days post-TLI. Mixed-chimeric mice contain more anti-donor Th2 CD4 cells and less anti-donor TC1 CD8 cells compared with nonchimeric mice and nonirradiated controls. Treatment with anti-IL-4 inhibits the development of mixed-chimerism ( <0.05), and these nonchimeric mice contain donor-reactive TC1 CD8 cells.
IL-4 plays a role in the development of mixed-chimerism, perhaps by inhibition of anti-donor TC1 CD8 cells or enhancement of anti-donor Th2 CD4 cells.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/00007890-200210150-00022</identifier><identifier>PMID: 12394849</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antibody Formation ; Biological and medical sciences ; Bone marrow, stem cells transplantation. Graft versus host reaction ; CD4 Lymphocyte Count ; CD4-CD8 Ratio ; Cytokines - metabolism ; Hematopoietic Stem Cell Transplantation ; Interleukin-4 - physiology ; Lymphatic Irradiation - adverse effects ; Lymphopenia - etiology ; Medical sciences ; Mice ; Mice, Inbred A ; Mice, Inbred BALB C ; T-Lymphocytes - metabolism ; T-Lymphocytes, Cytotoxic - metabolism ; Th2 Cells - metabolism ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Transplantation Chimera - physiology</subject><ispartof>Transplantation, 2002-10, Vol.74 (7), p.1021-1029</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-3fb12b1930b887b516f594683013f24a46502c131aadd508b6fa6d975ce667f93</citedby><cites>FETCH-LOGICAL-c422t-3fb12b1930b887b516f594683013f24a46502c131aadd508b6fa6d975ce667f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13978056$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12394849$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FIELD, Elizabeth H</creatorcontrib><creatorcontrib>ROUSE, Todd</creatorcontrib><title>Requirements for developing mixed-chimerism in nonmyeloablative total-lymphoid irradiated mice: Role of IL-4 and immunoredirection</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Adult mice treated with total-lymphoid irradiation (TLI) followed by hematopoietic cell transfer develop stable mixed-chimerism. The purpose of the study is to examine the requirements for the development of mixed-chimerism and characterize the immune responses associated with mixed-chimerism.
T-cell number and function were examined in spleens of TLI-treated mice at various times after the completion of TLI by fluorescence-activated cell sorter (FACS) analysis and enzyme-linked immunosorbent assay (ELISA). TLI-treated BALB/c mice were injected with CAF(1) spleen cells between 2 and 28 days after completing TLI, with or without concurrent anti-IL-4. The extent of mixed-chimerism was determined using multiparameter FACS analysis. Enzyme-linked immunosorbent spot (ELISPOT) assays were used to measure anti-donor CD4+ and CD8+ immune responses.
TLI treatment results in transient lymphopenia, sparing CD4 cells relative to CD8 cells, followed by gradual, partial recovery over 28 days. Day 2 post-TLI T cells produce more interleukin (IL)-4, but less IL-2, interferon (IFN)-gamma and IL-10, while day 28 post-TLI T cells produce more IFN-gamma relative to IL-4. More than 70% of mice develop mixed-chimerism when injected with CAF(1) cells at 2 days post-TLI, while none become chimeric if injected at 28 days post-TLI. Mixed-chimeric mice contain more anti-donor Th2 CD4 cells and less anti-donor TC1 CD8 cells compared with nonchimeric mice and nonirradiated controls. Treatment with anti-IL-4 inhibits the development of mixed-chimerism ( <0.05), and these nonchimeric mice contain donor-reactive TC1 CD8 cells.
IL-4 plays a role in the development of mixed-chimerism, perhaps by inhibition of anti-donor TC1 CD8 cells or enhancement of anti-donor Th2 CD4 cells.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antibody Formation</subject><subject>Biological and medical sciences</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-CD8 Ratio</subject><subject>Cytokines - metabolism</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Interleukin-4 - physiology</subject><subject>Lymphatic Irradiation - adverse effects</subject><subject>Lymphopenia - etiology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred A</subject><subject>Mice, Inbred BALB C</subject><subject>T-Lymphocytes - metabolism</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>Th2 Cells - metabolism</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Transplantation Chimera - physiology</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1rFTEQhoMo9lj9C5IbvYvmY_PlnZSqhQNC0eslm0xsZJOcJrvFc-svd2uPdm4GZp53Bh6EMKPvGLX6Pd1KG0sJp5QzyiQl24TzJ2jHpBiIooY-RTtKB0aYEPoMvej954ZIofVzdMa4sIMZ7A79vobbNTXIUJaOY204wB3M9ZDKD5zTLwjE36QMLfWMU8Gllnzc9m6a3ZLuAC91cTOZj_lwU1PAqTUXklsgbGkPH_B1nQHXiK_2ZMCubETOa6kNwvbVL6mWl-hZdHOHV6d-jr5_uvx28YXsv36-uvi4J37gfCEiToxPzAo6GaMnyVSUdlBGUCYiH9ygJOWeCeZcCJKaSUWngtXSg1I6WnGO3j7cPbR6u0Jfxpy6h3l2BeraR2aU4Fbdg-YB9K323iCOh5aya8eR0fHe__jP__jf__jX_xZ9ffqxThnCY_AkfAPenADXvZtjc8Wn_sgJqw2VSvwBoEyPGA</recordid><startdate>20021015</startdate><enddate>20021015</enddate><creator>FIELD, Elizabeth H</creator><creator>ROUSE, Todd</creator><general>Lippincott</general><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>7T5</scope><scope>H94</scope></search><sort><creationdate>20021015</creationdate><title>Requirements for developing mixed-chimerism in nonmyeloablative total-lymphoid irradiated mice: Role of IL-4 and immunoredirection</title><author>FIELD, Elizabeth H ; ROUSE, Todd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-3fb12b1930b887b516f594683013f24a46502c131aadd508b6fa6d975ce667f93</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>Antibody Formation</topic><topic>Biological and medical sciences</topic><topic>Bone marrow, stem cells transplantation. Graft versus host reaction</topic><topic>CD4 Lymphocyte Count</topic><topic>CD4-CD8 Ratio</topic><topic>Cytokines - metabolism</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Interleukin-4 - physiology</topic><topic>Lymphatic Irradiation - adverse effects</topic><topic>Lymphopenia - etiology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred A</topic><topic>Mice, Inbred BALB C</topic><topic>T-Lymphocytes - metabolism</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>Th2 Cells - metabolism</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Transplantation Chimera - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FIELD, Elizabeth H</creatorcontrib><creatorcontrib>ROUSE, Todd</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FIELD, Elizabeth H</au><au>ROUSE, Todd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Requirements for developing mixed-chimerism in nonmyeloablative total-lymphoid irradiated mice: Role of IL-4 and immunoredirection</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2002-10-15</date><risdate>2002</risdate><volume>74</volume><issue>7</issue><spage>1021</spage><epage>1029</epage><pages>1021-1029</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Adult mice treated with total-lymphoid irradiation (TLI) followed by hematopoietic cell transfer develop stable mixed-chimerism. The purpose of the study is to examine the requirements for the development of mixed-chimerism and characterize the immune responses associated with mixed-chimerism.
T-cell number and function were examined in spleens of TLI-treated mice at various times after the completion of TLI by fluorescence-activated cell sorter (FACS) analysis and enzyme-linked immunosorbent assay (ELISA). TLI-treated BALB/c mice were injected with CAF(1) spleen cells between 2 and 28 days after completing TLI, with or without concurrent anti-IL-4. The extent of mixed-chimerism was determined using multiparameter FACS analysis. Enzyme-linked immunosorbent spot (ELISPOT) assays were used to measure anti-donor CD4+ and CD8+ immune responses.
TLI treatment results in transient lymphopenia, sparing CD4 cells relative to CD8 cells, followed by gradual, partial recovery over 28 days. Day 2 post-TLI T cells produce more interleukin (IL)-4, but less IL-2, interferon (IFN)-gamma and IL-10, while day 28 post-TLI T cells produce more IFN-gamma relative to IL-4. More than 70% of mice develop mixed-chimerism when injected with CAF(1) cells at 2 days post-TLI, while none become chimeric if injected at 28 days post-TLI. Mixed-chimeric mice contain more anti-donor Th2 CD4 cells and less anti-donor TC1 CD8 cells compared with nonchimeric mice and nonirradiated controls. Treatment with anti-IL-4 inhibits the development of mixed-chimerism ( <0.05), and these nonchimeric mice contain donor-reactive TC1 CD8 cells.
IL-4 plays a role in the development of mixed-chimerism, perhaps by inhibition of anti-donor TC1 CD8 cells or enhancement of anti-donor Th2 CD4 cells.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>12394849</pmid><doi>10.1097/00007890-200210150-00022</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antibody Formation Biological and medical sciences Bone marrow, stem cells transplantation. Graft versus host reaction CD4 Lymphocyte Count CD4-CD8 Ratio Cytokines - metabolism Hematopoietic Stem Cell Transplantation Interleukin-4 - physiology Lymphatic Irradiation - adverse effects Lymphopenia - etiology Medical sciences Mice Mice, Inbred A Mice, Inbred BALB C T-Lymphocytes - metabolism T-Lymphocytes, Cytotoxic - metabolism Th2 Cells - metabolism Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation Chimera - physiology |
title | Requirements for developing mixed-chimerism in nonmyeloablative total-lymphoid irradiated mice: Role of IL-4 and immunoredirection |
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