Requirement for early donor cell chimerism during prolonged survival of murine skin allografts
Posttransplantation infusion of donor bone marrow cells (BMC) can prolong allograft survival in antilymphocyte antibody- (ALA) treated recipients. This study examined the hypothesis that chimerism of donor BMC origin contributes to allograft unresponsiveness. Survival of day 0 skin grafts from C3H (...
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| Veröffentlicht in: | Transplantation 2000-04, Vol.69 (8), p.1667-1675 |
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| creator | MASLI, S DE FAZIO, S. R GOZZO, J. J |
| description | Posttransplantation infusion of donor bone marrow cells (BMC) can prolong allograft survival in antilymphocyte antibody- (ALA) treated recipients. This study examined the hypothesis that chimerism of donor BMC origin contributes to allograft unresponsiveness.
Survival of day 0 skin grafts from C3H (H2k) donors was prolonged on ALA-treated B6AF1 mice by day +7 infusion of BMC from C3H or C3H-H2o2 (H2K(d)I(d)D(k)) mice. To test for functional chimerism, depletional anti-H2Kd antibody was injected at intervals after C3H-H2o2 BMC infusion. To confirm the persistence of active cells in the recipients, cells harvested from bone marrow of ALA- and C3H BMC-treated primary recipients were transferred to secondary ALA-treated recipients. Other recipients were infused on day +21 with additional donor BMC or light-density BMC that had been cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to promote the differentiation of dendritic cells (DC).
Injection of depletional antibody targeting infused BMC interrupted skin graft survival, whether the injection was made on day +7, 2 hr after BMC injection, or as late as day +28. Prolonged graft survival was transferred to secondary recipients with cells recovered from primary recipient marrow as long as 4 weeks after initial donor BMC treatment. Graft survival prolonged by day +7 BMC was further enhanced by infusion on day +21 of light density cultured BMC, although a second dose of unfractionated BMC was inactive. Repeated injection of cultured BMC at 2-week intervals after day +21 prolonged graft survival even further.
These data directly demonstrate that at least short-term donor BMC-derived microchimerism is required for prolonged allograft survival. The data further suggest that the active chimeric cells persist in recipient marrow. Finally, the beneficial effect of late infusion of cultured cells containing partially differentiated DC suggest that DC may be the active chimeric cells. |
| doi_str_mv | 10.1097/00007890-200004270-00024 |
| format | Article |
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Survival of day 0 skin grafts from C3H (H2k) donors was prolonged on ALA-treated B6AF1 mice by day +7 infusion of BMC from C3H or C3H-H2o2 (H2K(d)I(d)D(k)) mice. To test for functional chimerism, depletional anti-H2Kd antibody was injected at intervals after C3H-H2o2 BMC infusion. To confirm the persistence of active cells in the recipients, cells harvested from bone marrow of ALA- and C3H BMC-treated primary recipients were transferred to secondary ALA-treated recipients. Other recipients were infused on day +21 with additional donor BMC or light-density BMC that had been cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to promote the differentiation of dendritic cells (DC).
Injection of depletional antibody targeting infused BMC interrupted skin graft survival, whether the injection was made on day +7, 2 hr after BMC injection, or as late as day +28. Prolonged graft survival was transferred to secondary recipients with cells recovered from primary recipient marrow as long as 4 weeks after initial donor BMC treatment. Graft survival prolonged by day +7 BMC was further enhanced by infusion on day +21 of light density cultured BMC, although a second dose of unfractionated BMC was inactive. Repeated injection of cultured BMC at 2-week intervals after day +21 prolonged graft survival even further.
These data directly demonstrate that at least short-term donor BMC-derived microchimerism is required for prolonged allograft survival. The data further suggest that the active chimeric cells persist in recipient marrow. Finally, the beneficial effect of late infusion of cultured cells containing partially differentiated DC suggest that DC may be the active chimeric cells.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/00007890-200004270-00024</identifier><identifier>PMID: 10836379</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Animals ; Antibodies - therapeutic use ; Biological and medical sciences ; Bone Marrow Cells - immunology ; Bone Marrow Transplantation ; Chimera - physiology ; Dendritic Cells - transplantation ; Graft Survival - physiology ; Male ; Medical sciences ; Mice ; Mice, Inbred Strains ; Skin plastic surgery ; Skin Transplantation ; Stem Cell Transplantation ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Time Factors ; Tissue Donors ; Transplantation, Homologous</subject><ispartof>Transplantation, 2000-04, Vol.69 (8), p.1667-1675</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1490524$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10836379$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MASLI, S</creatorcontrib><creatorcontrib>DE FAZIO, S. R</creatorcontrib><creatorcontrib>GOZZO, J. J</creatorcontrib><title>Requirement for early donor cell chimerism during prolonged survival of murine skin allografts</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Posttransplantation infusion of donor bone marrow cells (BMC) can prolong allograft survival in antilymphocyte antibody- (ALA) treated recipients. This study examined the hypothesis that chimerism of donor BMC origin contributes to allograft unresponsiveness.
Survival of day 0 skin grafts from C3H (H2k) donors was prolonged on ALA-treated B6AF1 mice by day +7 infusion of BMC from C3H or C3H-H2o2 (H2K(d)I(d)D(k)) mice. To test for functional chimerism, depletional anti-H2Kd antibody was injected at intervals after C3H-H2o2 BMC infusion. To confirm the persistence of active cells in the recipients, cells harvested from bone marrow of ALA- and C3H BMC-treated primary recipients were transferred to secondary ALA-treated recipients. Other recipients were infused on day +21 with additional donor BMC or light-density BMC that had been cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to promote the differentiation of dendritic cells (DC).
Injection of depletional antibody targeting infused BMC interrupted skin graft survival, whether the injection was made on day +7, 2 hr after BMC injection, or as late as day +28. Prolonged graft survival was transferred to secondary recipients with cells recovered from primary recipient marrow as long as 4 weeks after initial donor BMC treatment. Graft survival prolonged by day +7 BMC was further enhanced by infusion on day +21 of light density cultured BMC, although a second dose of unfractionated BMC was inactive. Repeated injection of cultured BMC at 2-week intervals after day +21 prolonged graft survival even further.
These data directly demonstrate that at least short-term donor BMC-derived microchimerism is required for prolonged allograft survival. The data further suggest that the active chimeric cells persist in recipient marrow. Finally, the beneficial effect of late infusion of cultured cells containing partially differentiated DC suggest that DC may be the active chimeric cells.</description><subject>Animals</subject><subject>Antibodies - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - immunology</subject><subject>Bone Marrow Transplantation</subject><subject>Chimera - physiology</subject><subject>Dendritic Cells - transplantation</subject><subject>Graft Survival - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Skin plastic surgery</subject><subject>Skin Transplantation</subject><subject>Stem Cell Transplantation</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Time Factors</subject><subject>Tissue Donors</subject><subject>Transplantation, Homologous</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE9LAzEUxIMotla_guQg3laTTTYvOYr4DwqC6NWSzSY1mt1tk91Cv70pVjz6LjMwPx7DIIQpuaJEwTXJB1KRotw5XgIpspb8AE1pxXghiCSHaJojWlDGYIJOUvrMSMUAjtGEEskEAzVF7y92PfpoW9sN2PURWx3DFjd9l72xIWDz4VsbfWpxM0bfLfEq9qHvlrbBaYwbv9EB9w63u9Di9OU7rEPol1G7IZ2iI6dDsmd7naG3-7vX28di_vzwdHszL1algKEoQdkaSmmNUkoIapkE2RjjuJNcUdrUDUjnHGOOS15VpDZUMCO4qp2CGtgMXf78zeXWo03DovVpV193th_TAijlUnLyL0hB0DytyOD5Hhzr1jaLVfStjtvF73QZuNgDOhkdXNSd8emP44pUJWffKXR_sA</recordid><startdate>20000427</startdate><enddate>20000427</enddate><creator>MASLI, S</creator><creator>DE FAZIO, S. R</creator><creator>GOZZO, J. J</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20000427</creationdate><title>Requirement for early donor cell chimerism during prolonged survival of murine skin allografts</title><author>MASLI, S ; DE FAZIO, S. R ; GOZZO, J. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p267t-279eb728ec999661e3878dccf4f84911dbd78fff33f484550bc163c649bf97b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Antibodies - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - immunology</topic><topic>Bone Marrow Transplantation</topic><topic>Chimera - physiology</topic><topic>Dendritic Cells - transplantation</topic><topic>Graft Survival - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Skin plastic surgery</topic><topic>Skin Transplantation</topic><topic>Stem Cell Transplantation</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Time Factors</topic><topic>Tissue Donors</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MASLI, S</creatorcontrib><creatorcontrib>DE FAZIO, S. R</creatorcontrib><creatorcontrib>GOZZO, J. J</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MASLI, S</au><au>DE FAZIO, S. R</au><au>GOZZO, J. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Requirement for early donor cell chimerism during prolonged survival of murine skin allografts</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2000-04-27</date><risdate>2000</risdate><volume>69</volume><issue>8</issue><spage>1667</spage><epage>1675</epage><pages>1667-1675</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Posttransplantation infusion of donor bone marrow cells (BMC) can prolong allograft survival in antilymphocyte antibody- (ALA) treated recipients. This study examined the hypothesis that chimerism of donor BMC origin contributes to allograft unresponsiveness.
Survival of day 0 skin grafts from C3H (H2k) donors was prolonged on ALA-treated B6AF1 mice by day +7 infusion of BMC from C3H or C3H-H2o2 (H2K(d)I(d)D(k)) mice. To test for functional chimerism, depletional anti-H2Kd antibody was injected at intervals after C3H-H2o2 BMC infusion. To confirm the persistence of active cells in the recipients, cells harvested from bone marrow of ALA- and C3H BMC-treated primary recipients were transferred to secondary ALA-treated recipients. Other recipients were infused on day +21 with additional donor BMC or light-density BMC that had been cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to promote the differentiation of dendritic cells (DC).
Injection of depletional antibody targeting infused BMC interrupted skin graft survival, whether the injection was made on day +7, 2 hr after BMC injection, or as late as day +28. Prolonged graft survival was transferred to secondary recipients with cells recovered from primary recipient marrow as long as 4 weeks after initial donor BMC treatment. Graft survival prolonged by day +7 BMC was further enhanced by infusion on day +21 of light density cultured BMC, although a second dose of unfractionated BMC was inactive. Repeated injection of cultured BMC at 2-week intervals after day +21 prolonged graft survival even further.
These data directly demonstrate that at least short-term donor BMC-derived microchimerism is required for prolonged allograft survival. The data further suggest that the active chimeric cells persist in recipient marrow. Finally, the beneficial effect of late infusion of cultured cells containing partially differentiated DC suggest that DC may be the active chimeric cells.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>10836379</pmid><doi>10.1097/00007890-200004270-00024</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Antibodies - therapeutic use Biological and medical sciences Bone Marrow Cells - immunology Bone Marrow Transplantation Chimera - physiology Dendritic Cells - transplantation Graft Survival - physiology Male Medical sciences Mice Mice, Inbred Strains Skin plastic surgery Skin Transplantation Stem Cell Transplantation Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Time Factors Tissue Donors Transplantation, Homologous |
| title | Requirement for early donor cell chimerism during prolonged survival of murine skin allografts |
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