Generation of HIV-1–specific CD8+ cell responses following allogeneic hematopoietic cell transplantation
This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infus...
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| Veröffentlicht in: | Blood 2008-10, Vol.112 (8), p.3484-3487 |
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| creator | Woolfrey, Ann E. Malhotra, Uma Harrington, Robert D. McNevin, John Manley, Thomas J. Riddell, Stanley R. Coombs, Robert W. Appelbaum, Frederick R. Corey, Larry Storb, Rainer |
| description | This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1–specific CD8+ cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8+ T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1–specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593). |
| doi_str_mv | 10.1182/blood-2008-05-157511 |
| format | Article |
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A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1–specific CD8+ cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8+ T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1–specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2008-05-157511</identifier><identifier>PMID: 18698002</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adult ; Antiretroviral Therapy, Highly Active ; Biological and medical sciences ; CD8-Positive T-Lymphocytes - virology ; Cyclosporine - administration & dosage ; Epitopes - chemistry ; Hematologic and hematopoietic diseases ; Hematopoietic Stem Cell Transplantation ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV-1 - metabolism ; Human viral diseases ; Humans ; Immune System ; Immunosuppressive Agents - administration & dosage ; Infectious diseases ; Leukemia, Myeloid, Acute - complications ; Leukemia, Myeloid, Acute - drug therapy ; Male ; Medical sciences ; Mycophenolic Acid - administration & dosage ; Mycophenolic Acid - analogs & derivatives ; Transplantation ; Transplantation, Homologous ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>Blood, 2008-10, Vol.112 (8), p.3484-3487</ispartof><rights>2008 American Society of Hematology</rights><rights>2009 INIST-CNRS</rights><rights>2008 by The American Society of Hematology 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-63cbdd28ca51ab0f61df659ef857a42e765f15279a1cd5d2d0c8d3eafc04409d3</citedby><cites>FETCH-LOGICAL-c491t-63cbdd28ca51ab0f61df659ef857a42e765f15279a1cd5d2d0c8d3eafc04409d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27915,27916</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20791778$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18698002$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Woolfrey, Ann E.</creatorcontrib><creatorcontrib>Malhotra, Uma</creatorcontrib><creatorcontrib>Harrington, Robert D.</creatorcontrib><creatorcontrib>McNevin, John</creatorcontrib><creatorcontrib>Manley, Thomas J.</creatorcontrib><creatorcontrib>Riddell, Stanley R.</creatorcontrib><creatorcontrib>Coombs, Robert W.</creatorcontrib><creatorcontrib>Appelbaum, Frederick R.</creatorcontrib><creatorcontrib>Corey, Larry</creatorcontrib><creatorcontrib>Storb, Rainer</creatorcontrib><title>Generation of HIV-1–specific CD8+ cell responses following allogeneic hematopoietic cell transplantation</title><title>Blood</title><addtitle>Blood</addtitle><description>This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1–specific CD8+ cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8+ T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1–specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).</description><subject>Adult</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Biological and medical sciences</subject><subject>CD8-Positive T-Lymphocytes - virology</subject><subject>Cyclosporine - administration & dosage</subject><subject>Epitopes - chemistry</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1 - metabolism</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immune System</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Infectious diseases</subject><subject>Leukemia, Myeloid, Acute - complications</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mycophenolic Acid - administration & dosage</subject><subject>Mycophenolic Acid - analogs & derivatives</subject><subject>Transplantation</subject><subject>Transplantation, Homologous</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1uFDEQhS0EIkPgBgj1Bjaooexuu90bpGiAJFIkNsDW8tjliSOP3dg9Qey4AzfkJHh-lMCGlf--eq5Xj5DnFN5QKtnbVUjJtgxAtsBbygdO6QOyoJzVC2DwkCwAQLT9ONAT8qSUGwDad4w_JidUilFWaEFuzjFi1rNPsUmuubj82tLfP3-VCY133jTL9_J1YzCEJmOZUixYGpdCSN99XDe6btZVoILXuNFzmpLHuZ72FXPWsUxBx3mv_5Q8cjoUfHZcT8mXjx8-Ly_aq0_nl8uzq9b0I51b0ZmVtUwazalegRPUOsFHdJIPumc4CO6qyWHU1FhumQUjbYfaGeh7GG13St4ddKftaoPWYKyNBDVlv9H5h0raq39for9W63SrGBcjlbwKvDoK5PRti2VWG192jnTEtC1KjKJnHezA_gCanErJ6O4-oaB2Ial9SGoXkgKuDiHVshd_N3hfdEylAi-PgC5GB1fnaHy54xgMIx0Gee8U6zhvPWZVjMdo0PqMZlY2-f938gdrPbR0</recordid><startdate>20081015</startdate><enddate>20081015</enddate><creator>Woolfrey, Ann E.</creator><creator>Malhotra, Uma</creator><creator>Harrington, Robert D.</creator><creator>McNevin, John</creator><creator>Manley, Thomas J.</creator><creator>Riddell, Stanley R.</creator><creator>Coombs, Robert W.</creator><creator>Appelbaum, Frederick R.</creator><creator>Corey, Larry</creator><creator>Storb, Rainer</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>20081015</creationdate><title>Generation of HIV-1–specific CD8+ cell responses following allogeneic hematopoietic cell transplantation</title><author>Woolfrey, Ann E. ; Malhotra, Uma ; Harrington, Robert D. ; McNevin, John ; Manley, Thomas J. ; Riddell, Stanley R. ; Coombs, Robert W. ; Appelbaum, Frederick R. ; Corey, Larry ; Storb, Rainer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-63cbdd28ca51ab0f61df659ef857a42e765f15279a1cd5d2d0c8d3eafc04409d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Antiretroviral Therapy, Highly Active</topic><topic>Biological and medical sciences</topic><topic>CD8-Positive T-Lymphocytes - virology</topic><topic>Cyclosporine - administration & dosage</topic><topic>Epitopes - chemistry</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - drug therapy</topic><topic>HIV-1 - metabolism</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immune System</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Infectious diseases</topic><topic>Leukemia, Myeloid, Acute - complications</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mycophenolic Acid - administration & dosage</topic><topic>Mycophenolic Acid - analogs & derivatives</topic><topic>Transplantation</topic><topic>Transplantation, Homologous</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Woolfrey, Ann E.</creatorcontrib><creatorcontrib>Malhotra, Uma</creatorcontrib><creatorcontrib>Harrington, Robert D.</creatorcontrib><creatorcontrib>McNevin, John</creatorcontrib><creatorcontrib>Manley, Thomas J.</creatorcontrib><creatorcontrib>Riddell, Stanley R.</creatorcontrib><creatorcontrib>Coombs, Robert W.</creatorcontrib><creatorcontrib>Appelbaum, Frederick R.</creatorcontrib><creatorcontrib>Corey, Larry</creatorcontrib><creatorcontrib>Storb, Rainer</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Woolfrey, Ann E.</au><au>Malhotra, Uma</au><au>Harrington, Robert D.</au><au>McNevin, John</au><au>Manley, Thomas J.</au><au>Riddell, Stanley R.</au><au>Coombs, Robert W.</au><au>Appelbaum, Frederick R.</au><au>Corey, Larry</au><au>Storb, Rainer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation of HIV-1–specific CD8+ cell responses following allogeneic hematopoietic cell transplantation</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2008-10-15</date><risdate>2008</risdate><volume>112</volume><issue>8</issue><spage>3484</spage><epage>3487</epage><pages>3484-3487</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>This study tested whether donor-derived HIV-specific immune responses could be detected when viral replication was completely suppressed by the continuous administration of highly active antiretroviral therapy (HAART). A regimen of fludarabine and 200 cGy total body irradiation was followed by infusion of allogeneic donor peripheral blood cells and posttransplantation cyclosporine and mycophenolate mofetil. Viral load, lymphocyte counts, and HIV-1–specific CD8+ cell immune responses were compared before and after hematopoietic cell transplantation (HCT). Uninterrupted administration of HAART was feasible during nonmyeloablative conditioning and after HCT. The HIV RNA remained undetectable and no HIV-associated infections were observed. CD8+ T-cell responses targeting multiple epitopes were detected before HCT. After HCT a different pattern of donor-derived HIV-specific CTL responses emerged by day +80, presumably primed in vivo. We conclude that allogeneic HCT offers the unique ability to characterize de novo HIV-1–specific immune responses. This clinical trial was registered at ClinicalTrials.gov (identifier: NCT00112593).</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>18698002</pmid><doi>10.1182/blood-2008-05-157511</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Antiretroviral Therapy, Highly Active Biological and medical sciences CD8-Positive T-Lymphocytes - virology Cyclosporine - administration & dosage Epitopes - chemistry Hematologic and hematopoietic diseases Hematopoietic Stem Cell Transplantation HIV Infections - complications HIV Infections - drug therapy HIV-1 - metabolism Human viral diseases Humans Immune System Immunosuppressive Agents - administration & dosage Infectious diseases Leukemia, Myeloid, Acute - complications Leukemia, Myeloid, Acute - drug therapy Male Medical sciences Mycophenolic Acid - administration & dosage Mycophenolic Acid - analogs & derivatives Transplantation Transplantation, Homologous Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | Generation of HIV-1–specific CD8+ cell responses following allogeneic hematopoietic cell transplantation |
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