Characterization of Rabbit Antithymocyte Globulins-Induced CD25+ Regulatory T Cells From Cells of Patients With End-Stage Renal Disease
BACKGROUND.: Rabbit antithymocyte globulins (rATGs) are known to convert CD4CD25FoxP3 T cells from healthy individuals to CD4CD25FoxP3 T cells. In this study, we investigated the effect of rATG on the induction of regulatory T cells (Tregs) from blood cells of patients with end-stage renal disease w...
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| Veröffentlicht in: | Transplantation 2010-03, Vol.89 (6), p.655-666 |
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| creator | SEWGOBIND, Varsha D. K. D VAN DER LAAN, Luc J. W KHO, Marcia M. L KRAAIJEVELD, Rens KOREVAAR, Sander S VAN DAM, Thea IJZERMANS, Jan N. M WEIMAR, Willem BAAN, Carla C |
| description | BACKGROUND.: Rabbit antithymocyte globulins (rATGs) are known to convert CD4CD25FoxP3 T cells from healthy individuals to CD4CD25FoxP3 T cells. In this study, we investigated the effect of rATG on the induction of regulatory T cells (Tregs) from blood cells of patients with end-stage renal disease who are candidates for transplantation and rATG-induction therapy. The induced Tregs were analyzed and compared with naturally occurring CD4CD25FoxP3T cells. METHODS.: The CD25 T cells of pretransplant patients (n=7) and healthy controls (n=4) were stimulated with rATG or control rabbit immunoglobulins for 24 hr. The phenotype of induced Tregs was examined by flow cytometry, and their function was studied in the conventional suppression assay. Further characterization was performed by mRNA analyses. RESULTS.: After 24 hr, the percentage of CD4CD25FoxP3CD127 T cells and CD8CD25FoxP3CD127 T cells became higher in the rATG-treated samples compared with the rabbit immunoglobulin-treated samples (P |
| doi_str_mv | 10.1097/TP.0b013e3181c9cc7a |
| format | Article |
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K. D ; VAN DER LAAN, Luc J. W ; KHO, Marcia M. L ; KRAAIJEVELD, Rens ; KOREVAAR, Sander S ; VAN DAM, Thea ; IJZERMANS, Jan N. M ; WEIMAR, Willem ; BAAN, Carla C</creator><creatorcontrib>SEWGOBIND, Varsha D. K. D ; VAN DER LAAN, Luc J. W ; KHO, Marcia M. L ; KRAAIJEVELD, Rens ; KOREVAAR, Sander S ; VAN DAM, Thea ; IJZERMANS, Jan N. M ; WEIMAR, Willem ; BAAN, Carla C</creatorcontrib><description>BACKGROUND.: Rabbit antithymocyte globulins (rATGs) are known to convert CD4CD25FoxP3 T cells from healthy individuals to CD4CD25FoxP3 T cells. In this study, we investigated the effect of rATG on the induction of regulatory T cells (Tregs) from blood cells of patients with end-stage renal disease who are candidates for transplantation and rATG-induction therapy. The induced Tregs were analyzed and compared with naturally occurring CD4CD25FoxP3T cells. METHODS.: The CD25 T cells of pretransplant patients (n=7) and healthy controls (n=4) were stimulated with rATG or control rabbit immunoglobulins for 24 hr. The phenotype of induced Tregs was examined by flow cytometry, and their function was studied in the conventional suppression assay. Further characterization was performed by mRNA analyses. RESULTS.: After 24 hr, the percentage of CD4CD25FoxP3CD127 T cells and CD8CD25FoxP3CD127 T cells became higher in the rATG-treated samples compared with the rabbit immunoglobulin-treated samples (P<0.01). The rATG-induced CD25T cells, whether CD4 or CD8 inhibited the allogeneic responses of CD25 effector T cells as vigorously as natural CD25T cells. However, the proportion of FoxP3 within the top 2% rATG-induced CD4CD25T-cells was lower than within the natural CD4CD25T-cells (11%+/-2% vs. 95%+/-5%, P<0.01). The mRNA-expression levels of interleukin-27, interleukin-10, interferon-gamma, perforin, and granzyme B were markedly higher compared with natural CD25T-cells (all P=0.03), whereas CTLA4 (P=0.03), transforming growth factor-beta (P=0.02), and RORgammat (P=0.04) were lower. CONCLUSION.: rATG allows the induction of Tregs from patient peripheral blood mononuclear cell in vitro. In comparison with natural Tregs, the rATG-induced Tregs are phenotypically distinct but have similar regulatory activities. rATG may beneficially contribute to the mechanisms that control alloreactivity.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/TP.0b013e3181c9cc7a</identifier><identifier>PMID: 20164820</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Antilymphocyte Serum - immunology ; Biological and medical sciences ; Case-Control Studies ; Cells, Cultured ; Cytokines - genetics ; Cytotoxicity, Immunologic ; Dose-Response Relationship, Immunologic ; Flow Cytometry ; Forkhead Transcription Factors - metabolism ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Granzymes - genetics ; Humans ; Immunophenotyping - methods ; Interleukin-2 Receptor alpha Subunit - metabolism ; Interleukin-7 Receptor alpha Subunit - metabolism ; Kidney Failure, Chronic - immunology ; Kidney Failure, Chronic - surgery ; Kidney Transplantation ; Leukocytes, Mononuclear - immunology ; Medical sciences ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Perforin - genetics ; Phenotype ; Protein Binding ; Rabbits ; Renal failure ; RNA, Messenger - metabolism ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Regulatory - immunology ; Time Factors ; Tissue, organ and graft immunology</subject><ispartof>Transplantation, 2010-03, Vol.89 (6), p.655-666</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-fa3226b5f89aa86d86c64d1c5280f89ac98f6a7f3bd6cc4f3fde32f029dbd6ba3</citedby><cites>FETCH-LOGICAL-c411t-fa3226b5f89aa86d86c64d1c5280f89ac98f6a7f3bd6cc4f3fde32f029dbd6ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22545717$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20164820$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SEWGOBIND, Varsha D. K. D</creatorcontrib><creatorcontrib>VAN DER LAAN, Luc J. W</creatorcontrib><creatorcontrib>KHO, Marcia M. L</creatorcontrib><creatorcontrib>KRAAIJEVELD, Rens</creatorcontrib><creatorcontrib>KOREVAAR, Sander S</creatorcontrib><creatorcontrib>VAN DAM, Thea</creatorcontrib><creatorcontrib>IJZERMANS, Jan N. M</creatorcontrib><creatorcontrib>WEIMAR, Willem</creatorcontrib><creatorcontrib>BAAN, Carla C</creatorcontrib><title>Characterization of Rabbit Antithymocyte Globulins-Induced CD25+ Regulatory T Cells From Cells of Patients With End-Stage Renal Disease</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>BACKGROUND.: Rabbit antithymocyte globulins (rATGs) are known to convert CD4CD25FoxP3 T cells from healthy individuals to CD4CD25FoxP3 T cells. In this study, we investigated the effect of rATG on the induction of regulatory T cells (Tregs) from blood cells of patients with end-stage renal disease who are candidates for transplantation and rATG-induction therapy. The induced Tregs were analyzed and compared with naturally occurring CD4CD25FoxP3T cells. METHODS.: The CD25 T cells of pretransplant patients (n=7) and healthy controls (n=4) were stimulated with rATG or control rabbit immunoglobulins for 24 hr. The phenotype of induced Tregs was examined by flow cytometry, and their function was studied in the conventional suppression assay. Further characterization was performed by mRNA analyses. RESULTS.: After 24 hr, the percentage of CD4CD25FoxP3CD127 T cells and CD8CD25FoxP3CD127 T cells became higher in the rATG-treated samples compared with the rabbit immunoglobulin-treated samples (P<0.01). The rATG-induced CD25T cells, whether CD4 or CD8 inhibited the allogeneic responses of CD25 effector T cells as vigorously as natural CD25T cells. However, the proportion of FoxP3 within the top 2% rATG-induced CD4CD25T-cells was lower than within the natural CD4CD25T-cells (11%+/-2% vs. 95%+/-5%, P<0.01). The mRNA-expression levels of interleukin-27, interleukin-10, interferon-gamma, perforin, and granzyme B were markedly higher compared with natural CD25T-cells (all P=0.03), whereas CTLA4 (P=0.03), transforming growth factor-beta (P=0.02), and RORgammat (P=0.04) were lower. CONCLUSION.: rATG allows the induction of Tregs from patient peripheral blood mononuclear cell in vitro. In comparison with natural Tregs, the rATG-induced Tregs are phenotypically distinct but have similar regulatory activities. rATG may beneficially contribute to the mechanisms that control alloreactivity.</description><subject>Animals</subject><subject>Antilymphocyte Serum - immunology</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>Cells, Cultured</subject><subject>Cytokines - genetics</subject><subject>Cytotoxicity, Immunologic</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Granzymes - genetics</subject><subject>Humans</subject><subject>Immunophenotyping - methods</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Interleukin-7 Receptor alpha Subunit - metabolism</subject><subject>Kidney Failure, Chronic - immunology</subject><subject>Kidney Failure, Chronic - surgery</subject><subject>Kidney Transplantation</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Perforin - genetics</subject><subject>Phenotype</subject><subject>Protein Binding</subject><subject>Rabbits</subject><subject>Renal failure</subject><subject>RNA, Messenger - metabolism</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Time Factors</subject><subject>Tissue, organ and graft immunology</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctq3DAUhkVpaCZpn6BQtCldBCe62JK8DM6lgUCGZEqX5liXxMWWUkleTF-gr10NmbbQTVcSh-__OJwfofeUnFLSyrPN-pQMhHLLqaK61VrCK7SiDa8rQRR5jVaE1LSinMtDdJTSN0JIw6V8gw4ZoaJWjKzQz-4JIuhs4_gD8hg8Dg7fwzCMGZ_7POan7Rz0Nlt8PYVhmUafqhtvFm0N7i5Yc4Lv7eMyQQ5xize4s9OU8FUM8_5bbOvitT4n_LXY8KU31UOGR1uCHiZ8MSYLyb5FBw6mZN_t32P05epy032ubu-ub7rz20rXlObKAWdMDI1TLYASRgktakN1wxTZzXSrnADp-GCE1rXjzljOHGGtKZMB-DH69OJ9juH7YlPu5zHpsip4G5bUy6ZuOGs4_T9Z7toqKXYkfyF1DClF6_rnOM4Qtz0l_a6qfrPu_62qpD7s_cswW_Mn87ubAnzcA5A0TC6C12P6y7GyqqSS_wJzMJ7M</recordid><startdate>20100327</startdate><enddate>20100327</enddate><creator>SEWGOBIND, Varsha D. K. D</creator><creator>VAN DER LAAN, Luc J. W</creator><creator>KHO, Marcia M. L</creator><creator>KRAAIJEVELD, Rens</creator><creator>KOREVAAR, Sander S</creator><creator>VAN DAM, Thea</creator><creator>IJZERMANS, Jan N. M</creator><creator>WEIMAR, Willem</creator><creator>BAAN, Carla C</creator><general>Lippincott Williams & Wilkins</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>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20100327</creationdate><title>Characterization of Rabbit Antithymocyte Globulins-Induced CD25+ Regulatory T Cells From Cells of Patients With End-Stage Renal Disease</title><author>SEWGOBIND, Varsha D. K. D ; VAN DER LAAN, Luc J. W ; KHO, Marcia M. L ; KRAAIJEVELD, Rens ; KOREVAAR, Sander S ; VAN DAM, Thea ; IJZERMANS, Jan N. 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Psychology</topic><topic>Fundamental immunology</topic><topic>Granzymes - genetics</topic><topic>Humans</topic><topic>Immunophenotyping - methods</topic><topic>Interleukin-2 Receptor alpha Subunit - metabolism</topic><topic>Interleukin-7 Receptor alpha Subunit - metabolism</topic><topic>Kidney Failure, Chronic - immunology</topic><topic>Kidney Failure, Chronic - surgery</topic><topic>Kidney Transplantation</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Perforin - genetics</topic><topic>Phenotype</topic><topic>Protein Binding</topic><topic>Rabbits</topic><topic>Renal failure</topic><topic>RNA, Messenger - metabolism</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Time Factors</topic><topic>Tissue, organ and graft immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SEWGOBIND, Varsha D. K. D</creatorcontrib><creatorcontrib>VAN DER LAAN, Luc J. W</creatorcontrib><creatorcontrib>KHO, Marcia M. L</creatorcontrib><creatorcontrib>KRAAIJEVELD, Rens</creatorcontrib><creatorcontrib>KOREVAAR, Sander S</creatorcontrib><creatorcontrib>VAN DAM, Thea</creatorcontrib><creatorcontrib>IJZERMANS, Jan N. M</creatorcontrib><creatorcontrib>WEIMAR, Willem</creatorcontrib><creatorcontrib>BAAN, Carla C</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>MEDLINE - Academic</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>SEWGOBIND, Varsha D. K. D</au><au>VAN DER LAAN, Luc J. W</au><au>KHO, Marcia M. L</au><au>KRAAIJEVELD, Rens</au><au>KOREVAAR, Sander S</au><au>VAN DAM, Thea</au><au>IJZERMANS, Jan N. M</au><au>WEIMAR, Willem</au><au>BAAN, Carla C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of Rabbit Antithymocyte Globulins-Induced CD25+ Regulatory T Cells From Cells of Patients With End-Stage Renal Disease</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2010-03-27</date><risdate>2010</risdate><volume>89</volume><issue>6</issue><spage>655</spage><epage>666</epage><pages>655-666</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>BACKGROUND.: Rabbit antithymocyte globulins (rATGs) are known to convert CD4CD25FoxP3 T cells from healthy individuals to CD4CD25FoxP3 T cells. In this study, we investigated the effect of rATG on the induction of regulatory T cells (Tregs) from blood cells of patients with end-stage renal disease who are candidates for transplantation and rATG-induction therapy. The induced Tregs were analyzed and compared with naturally occurring CD4CD25FoxP3T cells. METHODS.: The CD25 T cells of pretransplant patients (n=7) and healthy controls (n=4) were stimulated with rATG or control rabbit immunoglobulins for 24 hr. The phenotype of induced Tregs was examined by flow cytometry, and their function was studied in the conventional suppression assay. Further characterization was performed by mRNA analyses. RESULTS.: After 24 hr, the percentage of CD4CD25FoxP3CD127 T cells and CD8CD25FoxP3CD127 T cells became higher in the rATG-treated samples compared with the rabbit immunoglobulin-treated samples (P<0.01). The rATG-induced CD25T cells, whether CD4 or CD8 inhibited the allogeneic responses of CD25 effector T cells as vigorously as natural CD25T cells. However, the proportion of FoxP3 within the top 2% rATG-induced CD4CD25T-cells was lower than within the natural CD4CD25T-cells (11%+/-2% vs. 95%+/-5%, P<0.01). The mRNA-expression levels of interleukin-27, interleukin-10, interferon-gamma, perforin, and granzyme B were markedly higher compared with natural CD25T-cells (all P=0.03), whereas CTLA4 (P=0.03), transforming growth factor-beta (P=0.02), and RORgammat (P=0.04) were lower. CONCLUSION.: rATG allows the induction of Tregs from patient peripheral blood mononuclear cell in vitro. In comparison with natural Tregs, the rATG-induced Tregs are phenotypically distinct but have similar regulatory activities. rATG may beneficially contribute to the mechanisms that control alloreactivity.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>20164820</pmid><doi>10.1097/TP.0b013e3181c9cc7a</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Transplantation, 2010-03, Vol.89 (6), p.655-666 |
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| subjects | Animals Antilymphocyte Serum - immunology Biological and medical sciences Case-Control Studies Cells, Cultured Cytokines - genetics Cytotoxicity, Immunologic Dose-Response Relationship, Immunologic Flow Cytometry Forkhead Transcription Factors - metabolism Fundamental and applied biological sciences. Psychology Fundamental immunology Granzymes - genetics Humans Immunophenotyping - methods Interleukin-2 Receptor alpha Subunit - metabolism Interleukin-7 Receptor alpha Subunit - metabolism Kidney Failure, Chronic - immunology Kidney Failure, Chronic - surgery Kidney Transplantation Leukocytes, Mononuclear - immunology Medical sciences Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Perforin - genetics Phenotype Protein Binding Rabbits Renal failure RNA, Messenger - metabolism Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Regulatory - immunology Time Factors Tissue, organ and graft immunology |
| title | Characterization of Rabbit Antithymocyte Globulins-Induced CD25+ Regulatory T Cells From Cells of Patients With End-Stage Renal Disease |
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