Possible Role of Minor H Antigens in the Persistence of Donor Chimerism after Stem Cell Transplantation; Relevance for Sustained Leukemia Remission: e0119595
Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincide...
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creator | Torren, R vander Hensbergen, Yvette van Luther, Susanne Aghai, Zohara Rychnavska, Zuzana Stachova Slot, Manon Scherjon, Sicco Kroger, Nicolaus Ganser, Arnold Weissinger, Eva M |
description | Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT. |
doi_str_mv | 10.1371/journal.pone.0119595 |
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However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.</description><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119595</identifier><language>eng</language><ispartof>PloS one, 2015-03, Vol.10 (3)</ispartof><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>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>Torren, R vander</creatorcontrib><creatorcontrib>Hensbergen, Yvette van</creatorcontrib><creatorcontrib>Luther, Susanne</creatorcontrib><creatorcontrib>Aghai, Zohara</creatorcontrib><creatorcontrib>Rychnavska, Zuzana Stachova</creatorcontrib><creatorcontrib>Slot, Manon</creatorcontrib><creatorcontrib>Scherjon, Sicco</creatorcontrib><creatorcontrib>Kroger, Nicolaus</creatorcontrib><creatorcontrib>Ganser, Arnold</creatorcontrib><creatorcontrib>Weissinger, Eva M</creatorcontrib><title>Possible Role of Minor H Antigens in the Persistence of Donor Chimerism after Stem Cell Transplantation; Relevance for Sustained Leukemia Remission: e0119595</title><title>PloS one</title><description>Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.</description><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqVjkFOwzAQRS0kJArtDVjMkk2DHStuAysUQF2AVLXdV6ZMqIszDh6H23BXXNQLsPl_857-F-JayULpmbo9hCGS9UUfCAupVF3V1ZkYqVqXU1NKfSEumQ9SVnpuzEj8LAOze_MIq5AjtPDqKERYwAMl94HE4AjSHmGJkR0npN0f9hiOWLN3HUbHHdg2YYR1wg4a9B420RL33lKyyQW6hxV6_LZHu83ieuBkHeE7vODwiZ2zGehc_hLoDvB0fCzOW-sZJ6e-EjfPT5tmMe1j-BqQ0zYruzxnCcPAW2XMvDS6nkn9D_QXOKFlKw</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Torren, R vander</creator><creator>Hensbergen, Yvette van</creator><creator>Luther, Susanne</creator><creator>Aghai, Zohara</creator><creator>Rychnavska, Zuzana Stachova</creator><creator>Slot, Manon</creator><creator>Scherjon, Sicco</creator><creator>Kroger, Nicolaus</creator><creator>Ganser, Arnold</creator><creator>Weissinger, Eva M</creator><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20150301</creationdate><title>Possible Role of Minor H Antigens in the Persistence of Donor Chimerism after Stem Cell Transplantation; Relevance for Sustained Leukemia Remission: e0119595</title><author>Torren, R vander ; Hensbergen, Yvette van ; Luther, Susanne ; Aghai, Zohara ; Rychnavska, Zuzana Stachova ; Slot, Manon ; Scherjon, Sicco ; Kroger, Nicolaus ; Ganser, Arnold ; Weissinger, Eva M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_16682639703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Torren, R vander</creatorcontrib><creatorcontrib>Hensbergen, Yvette van</creatorcontrib><creatorcontrib>Luther, Susanne</creatorcontrib><creatorcontrib>Aghai, Zohara</creatorcontrib><creatorcontrib>Rychnavska, Zuzana Stachova</creatorcontrib><creatorcontrib>Slot, Manon</creatorcontrib><creatorcontrib>Scherjon, Sicco</creatorcontrib><creatorcontrib>Kroger, Nicolaus</creatorcontrib><creatorcontrib>Ganser, Arnold</creatorcontrib><creatorcontrib>Weissinger, Eva M</creatorcontrib><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torren, R vander</au><au>Hensbergen, Yvette van</au><au>Luther, Susanne</au><au>Aghai, Zohara</au><au>Rychnavska, Zuzana Stachova</au><au>Slot, Manon</au><au>Scherjon, Sicco</au><au>Kroger, Nicolaus</au><au>Ganser, Arnold</au><au>Weissinger, Eva M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Possible Role of Minor H Antigens in the Persistence of Donor Chimerism after Stem Cell Transplantation; Relevance for Sustained Leukemia Remission: e0119595</atitle><jtitle>PloS one</jtitle><date>2015-03-01</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><eissn>1932-6203</eissn><abstract>Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT). However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags) are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs) were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.</abstract><doi>10.1371/journal.pone.0119595</doi></addata></record> |
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title | Possible Role of Minor H Antigens in the Persistence of Donor Chimerism after Stem Cell Transplantation; Relevance for Sustained Leukemia Remission: e0119595 |
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