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
Hauptverfasser: FIELD, Elizabeth H, ROUSE, Todd
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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 (
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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 ( &lt;0.05), and these nonchimeric mice contain donor-reactive TC1 CD8 cells. 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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 ( &lt;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. 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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 ( &lt;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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