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HY Immune Tolerance Is Common in Women without Male Offspring

BACKGROUND: Sex difference is an established risk factor for hematopoietic stem cell transplantation (HSCT)-related complications like graft versus host disease (GVHD). CD8(pos) cytotoxic T cells specific for Y chromosome-encoded minor Histocompatibility antigens (HY) play an important role therein....

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Autores principales: Dierselhuis, Miranda P., Jankowska-Gan, Ewa, Blokland, Els, Pool, Jos, Burlingham, William J., van Halteren, Astrid G. S., Goulmy, Els
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960116/
https://www.ncbi.nlm.nih.gov/pubmed/24646895
http://dx.doi.org/10.1371/journal.pone.0091274
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author Dierselhuis, Miranda P.
Jankowska-Gan, Ewa
Blokland, Els
Pool, Jos
Burlingham, William J.
van Halteren, Astrid G. S.
Goulmy, Els
author_facet Dierselhuis, Miranda P.
Jankowska-Gan, Ewa
Blokland, Els
Pool, Jos
Burlingham, William J.
van Halteren, Astrid G. S.
Goulmy, Els
author_sort Dierselhuis, Miranda P.
collection PubMed
description BACKGROUND: Sex difference is an established risk factor for hematopoietic stem cell transplantation (HSCT)-related complications like graft versus host disease (GVHD). CD8(pos) cytotoxic T cells specific for Y chromosome-encoded minor Histocompatibility antigens (HY) play an important role therein. Prior to HSC donation, female donors may encounter HY antigens through fetomaternal or transmaternal cell flow, potentially leading to the induction of HY-specific cytotoxic or regulatory immune responses. Whether HY priming occurs independent of parity, and whether HY priming is dependent on the presence of male microchimerism, is as yet unknown. METHODS: We investigated the presence of HY-specific regulatory T cells (Treg) and male microchimerism in 45 healthy women with a fully documented pregnancy and family history. HY peptide-induced linked suppression, a commonly reported functional feature of CD4(pos) and CD8(pos) Treg, was measured by trans vivo Delayed Type Hypersensitivity testing. As source of HY antigens, male microchimerism was analyzed by real-time PCR and defined by the presence of male DNA in at least one purified leukocyte cell type. RESULTS: HLA class I or class II restricted HY-specific Treg were detected in 26/42 (62%) women eligible for analysis. The prevalence of HY-specific Treg was significantly higher in women who had never given birth to sons than in women with male offspring (p = 0.004). Male microchimerism could be detected in 24 out of 45 (53%) women but did not correlate with the presence of HY specific Treg. CONCLUSIONS: HY-specific Treg in women with male offspring have been described previously. Here we show for the first time that, in fact, HY specific Treg are more common in nulliparous women and in parous women with female offspring. Their presence is independent of the presence of male microchimerism. Whether HY-specific Treg presence in female stem cell grafts might decrease the GVHD incidence in male HSCT recipients needs to be investigated.
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spelling pubmed-39601162014-03-24 HY Immune Tolerance Is Common in Women without Male Offspring Dierselhuis, Miranda P. Jankowska-Gan, Ewa Blokland, Els Pool, Jos Burlingham, William J. van Halteren, Astrid G. S. Goulmy, Els PLoS One Research Article BACKGROUND: Sex difference is an established risk factor for hematopoietic stem cell transplantation (HSCT)-related complications like graft versus host disease (GVHD). CD8(pos) cytotoxic T cells specific for Y chromosome-encoded minor Histocompatibility antigens (HY) play an important role therein. Prior to HSC donation, female donors may encounter HY antigens through fetomaternal or transmaternal cell flow, potentially leading to the induction of HY-specific cytotoxic or regulatory immune responses. Whether HY priming occurs independent of parity, and whether HY priming is dependent on the presence of male microchimerism, is as yet unknown. METHODS: We investigated the presence of HY-specific regulatory T cells (Treg) and male microchimerism in 45 healthy women with a fully documented pregnancy and family history. HY peptide-induced linked suppression, a commonly reported functional feature of CD4(pos) and CD8(pos) Treg, was measured by trans vivo Delayed Type Hypersensitivity testing. As source of HY antigens, male microchimerism was analyzed by real-time PCR and defined by the presence of male DNA in at least one purified leukocyte cell type. RESULTS: HLA class I or class II restricted HY-specific Treg were detected in 26/42 (62%) women eligible for analysis. The prevalence of HY-specific Treg was significantly higher in women who had never given birth to sons than in women with male offspring (p = 0.004). Male microchimerism could be detected in 24 out of 45 (53%) women but did not correlate with the presence of HY specific Treg. CONCLUSIONS: HY-specific Treg in women with male offspring have been described previously. Here we show for the first time that, in fact, HY specific Treg are more common in nulliparous women and in parous women with female offspring. Their presence is independent of the presence of male microchimerism. Whether HY-specific Treg presence in female stem cell grafts might decrease the GVHD incidence in male HSCT recipients needs to be investigated. Public Library of Science 2014-03-19 /pmc/articles/PMC3960116/ /pubmed/24646895 http://dx.doi.org/10.1371/journal.pone.0091274 Text en © 2014 Dierselhuis et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dierselhuis, Miranda P.
Jankowska-Gan, Ewa
Blokland, Els
Pool, Jos
Burlingham, William J.
van Halteren, Astrid G. S.
Goulmy, Els
HY Immune Tolerance Is Common in Women without Male Offspring
title HY Immune Tolerance Is Common in Women without Male Offspring
title_full HY Immune Tolerance Is Common in Women without Male Offspring
title_fullStr HY Immune Tolerance Is Common in Women without Male Offspring
title_full_unstemmed HY Immune Tolerance Is Common in Women without Male Offspring
title_short HY Immune Tolerance Is Common in Women without Male Offspring
title_sort hy immune tolerance is common in women without male offspring
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960116/
https://www.ncbi.nlm.nih.gov/pubmed/24646895
http://dx.doi.org/10.1371/journal.pone.0091274
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