Short-term anti-CD25 monoclonal antibody administration down-regulated CD25 expression without eliminating the neogenetic functional regulatory T cells in kidney transplantation

CD4⁺CD25⁺ forkhead box P3 (FoxP3)⁺regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferatio...

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Veröffentlicht in:Clinical and experimental immunology 2009-03, Vol.155 (3), p.496-503
Hauptverfasser: Wang, Z, Shi, B.-Y, Qian, Y.-Y, Cai, M, Wang, Q
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creator Wang, Z
Shi, B.-Y
Qian, Y.-Y
Cai, M
Wang, Q
description CD4⁺CD25⁺ forkhead box P3 (FoxP3)⁺regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and Treg cells. Basiliximab (Simulect[trade mark sign]), a chimeric monoclonal antibody directed against the α-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of Treg cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the Treg cells in renal recipients. Basiliximab decreased the percentage of CD4⁺CD25⁺T cells, but failed to influence the percentage of CD4⁺FoxP3⁺ Treg cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4⁺CD25⁺ T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of Treg cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional Treg population may not be influenced by short-term basiliximab treatment.
doi_str_mv 10.1111/j.1365-2249.2008.03847.x
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It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and Treg cells. Basiliximab (Simulect[trade mark sign]), a chimeric monoclonal antibody directed against the α-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of Treg cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the Treg cells in renal recipients. Basiliximab decreased the percentage of CD4⁺CD25⁺T cells, but failed to influence the percentage of CD4⁺FoxP3⁺ Treg cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4⁺CD25⁺ T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of Treg cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional Treg population may not be influenced by short-term basiliximab treatment.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1111/j.1365-2249.2008.03847.x</identifier><identifier>PMID: 19141125</identifier><identifier>CODEN: CEXIAL</identifier><language>eng</language><publisher>Oxford, UK: Oxford, UK : Blackwell Publishing Ltd</publisher><subject>Adult ; Analytical, structural and metabolic biochemistry ; Antibodies, Monoclonal - therapeutic use ; basiliximab ; Biological and medical sciences ; Biomarkers - analysis ; CD4 Antigens - analysis ; CD4 Antigens - immunology ; CD4+CD25+FoxP3+ Treg cells ; CD4⁺CD25⁺FoxP3⁺ Treg cells ; Cell Proliferation - drug effects ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Forkhead Transcription Factors - analysis ; Forkhead Transcription Factors - immunology ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Graft Survival ; Humans ; IL-2 ; IL-2R ; Immunosuppressive Agents - therapeutic use ; Interferon-gamma - analysis ; Interleukin-2 - metabolism ; Interleukin-2 Receptor alpha Subunit - analysis ; Interleukin-2 Receptor alpha Subunit - immunology ; kidney transplant ; kidney transplantation ; Kidney Transplantation - immunology ; Lymphocyte Culture Test, Mixed ; Male ; Prospective Studies ; Receptors, Interleukin-2 - metabolism ; Recombinant Fusion Proteins - therapeutic use ; Statistics, Nonparametric ; T-Lymphocytes, Regulatory - immunology ; Transplantation ; Transplantation Tolerance ; Transplantation, Homologous</subject><ispartof>Clinical and experimental immunology, 2009-03, Vol.155 (3), p.496-503</ispartof><rights>2009 British Society for Immunology</rights><rights>2009 INIST-CNRS</rights><rights>2009 British Society for Immunology 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5887-46e3bfc9b9278e2ade4c12ddb2d5702b1113effc285f6ef6ffd1e0b59eb644d3</citedby><cites>FETCH-LOGICAL-c5887-46e3bfc9b9278e2ade4c12ddb2d5702b1113effc285f6ef6ffd1e0b59eb644d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669526/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669526/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=21108268$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19141125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Z</creatorcontrib><creatorcontrib>Shi, B.-Y</creatorcontrib><creatorcontrib>Qian, Y.-Y</creatorcontrib><creatorcontrib>Cai, M</creatorcontrib><creatorcontrib>Wang, Q</creatorcontrib><title>Short-term anti-CD25 monoclonal antibody administration down-regulated CD25 expression without eliminating the neogenetic functional regulatory T cells in kidney transplantation</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>CD4⁺CD25⁺ forkhead box P3 (FoxP3)⁺regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and Treg cells. Basiliximab (Simulect[trade mark sign]), a chimeric monoclonal antibody directed against the α-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of Treg cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the Treg cells in renal recipients. Basiliximab decreased the percentage of CD4⁺CD25⁺T cells, but failed to influence the percentage of CD4⁺FoxP3⁺ Treg cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4⁺CD25⁺ T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of Treg cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional Treg population may not be influenced by short-term basiliximab treatment.</description><subject>Adult</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>basiliximab</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - analysis</subject><subject>CD4 Antigens - analysis</subject><subject>CD4 Antigens - immunology</subject><subject>CD4+CD25+FoxP3+ Treg cells</subject><subject>CD4⁺CD25⁺FoxP3⁺ Treg cells</subject><subject>Cell Proliferation - drug effects</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors - analysis</subject><subject>Forkhead Transcription Factors - immunology</subject><subject>Fundamental and applied biological sciences. 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Psychology</topic><topic>Gene Expression</topic><topic>Graft Survival</topic><topic>Humans</topic><topic>IL-2</topic><topic>IL-2R</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Interferon-gamma - analysis</topic><topic>Interleukin-2 - metabolism</topic><topic>Interleukin-2 Receptor alpha Subunit - analysis</topic><topic>Interleukin-2 Receptor alpha Subunit - immunology</topic><topic>kidney transplant</topic><topic>kidney transplantation</topic><topic>Kidney Transplantation - immunology</topic><topic>Lymphocyte Culture Test, Mixed</topic><topic>Male</topic><topic>Prospective Studies</topic><topic>Receptors, Interleukin-2 - metabolism</topic><topic>Recombinant Fusion Proteins - therapeutic use</topic><topic>Statistics, Nonparametric</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Transplantation</topic><topic>Transplantation Tolerance</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Z</creatorcontrib><creatorcontrib>Shi, B.-Y</creatorcontrib><creatorcontrib>Qian, Y.-Y</creatorcontrib><creatorcontrib>Cai, M</creatorcontrib><creatorcontrib>Wang, Q</creatorcontrib><collection>AGRIS</collection><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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Z</au><au>Shi, B.-Y</au><au>Qian, Y.-Y</au><au>Cai, M</au><au>Wang, Q</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Short-term anti-CD25 monoclonal antibody administration down-regulated CD25 expression without eliminating the neogenetic functional regulatory T cells in kidney transplantation</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2009-03</date><risdate>2009</risdate><volume>155</volume><issue>3</issue><spage>496</spage><epage>503</epage><pages>496-503</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><coden>CEXIAL</coden><abstract>CD4⁺CD25⁺ forkhead box P3 (FoxP3)⁺regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and Treg cells. Basiliximab (Simulect[trade mark sign]), a chimeric monoclonal antibody directed against the α-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of Treg cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the Treg cells in renal recipients. Basiliximab decreased the percentage of CD4⁺CD25⁺T cells, but failed to influence the percentage of CD4⁺FoxP3⁺ Treg cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4⁺CD25⁺ T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of Treg cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional Treg population may not be influenced by short-term basiliximab treatment.</abstract><cop>Oxford, UK</cop><pub>Oxford, UK : Blackwell Publishing Ltd</pub><pmid>19141125</pmid><doi>10.1111/j.1365-2249.2008.03847.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); PubMed Central; Alma/SFX Local Collection
subjects Adult
Analytical, structural and metabolic biochemistry
Antibodies, Monoclonal - therapeutic use
basiliximab
Biological and medical sciences
Biomarkers - analysis
CD4 Antigens - analysis
CD4 Antigens - immunology
CD4+CD25+FoxP3+ Treg cells
CD4⁺CD25⁺FoxP3⁺ Treg cells
Cell Proliferation - drug effects
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Forkhead Transcription Factors - analysis
Forkhead Transcription Factors - immunology
Fundamental and applied biological sciences. Psychology
Gene Expression
Graft Survival
Humans
IL-2
IL-2R
Immunosuppressive Agents - therapeutic use
Interferon-gamma - analysis
Interleukin-2 - metabolism
Interleukin-2 Receptor alpha Subunit - analysis
Interleukin-2 Receptor alpha Subunit - immunology
kidney transplant
kidney transplantation
Kidney Transplantation - immunology
Lymphocyte Culture Test, Mixed
Male
Prospective Studies
Receptors, Interleukin-2 - metabolism
Recombinant Fusion Proteins - therapeutic use
Statistics, Nonparametric
T-Lymphocytes, Regulatory - immunology
Transplantation
Transplantation Tolerance
Transplantation, Homologous
title Short-term anti-CD25 monoclonal antibody administration down-regulated CD25 expression without eliminating the neogenetic functional regulatory T cells in kidney transplantation
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