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Selection and Characterisation of Minor Histocompatibility Antigen-Specific Regulatory T Cells in Fully HLA-Matched Setting for GVHD Therapy

dc.contributor.authorCarolina Paulino, Pacini
dc.contributor.authorAzevedo, Rita I.
dc.contributor.authorRamalhete, Luís
dc.contributor.authorLainé, Hugo A.J.
dc.contributor.authorSoares, Maria V.D.
dc.contributor.authorLacerda, João F.
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutioniNOVA4Health - pólo NMS
dc.contributor.pblWiley-VCH Verlag
dc.date.accessioned2026-01-14T15:55:28Z
dc.date.available2026-01-14T15:55:28Z
dc.date.issued2025-12
dc.descriptionPublisher Copyright: © 2025 The Author(s). European Journal of Immunology published by Wiley-VCH GmbH.
dc.description.abstractGraft-versus-host disease is mediated by donor-derived T cells reactive against the recipient's broadly expressed minor histocompatibility antigens (mHA). Regulatory T cells (Treg) have been explored as a therapeutic approach for chronic GVHD (cGVHD). The promising results from polyclonal Treg trials in this setting have led us to develop a Treg product specific for mismatched minor antigens between patient and donor (mTreg), circumventing broad immune suppression risks. HLA-matched siblings of opposite sexes were used to obtain the sister's CD4+CD25hiCD127low Treg for co-culture with the respective brother's dendritic cells as a source of mismatched mHA. We have established the optimal culture conditions resulting in the highest mTreg proliferation and viability. Comprehensive phenotyping during the ex vivo selection shows PD-1, CTLA-4, CD39 and HLA-DR expression. Transcriptomic analysis revealed a switch in metabolic process, and up-regulation of functional Treg genes. Furthermore, mTreg possess specific and potent suppressive activity, in which there is a dependency on cell-to-cell contact and a role for HLA class II expression on mTreg. This protocol would allow the generation of Treg specific to an array of mHA from the recipient's healthy tissues, likely providing a directed and strong suppression of cGVHD.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2570656
dc.identifier.doi10.1002/eji.70096
dc.identifier.issn0014-2980
dc.identifier.otherPURE: 149009941
dc.identifier.otherPURE UUID: 52af33b4-f825-46e0-97ad-bcb2460b8b08
dc.identifier.otherScopus: 105025171186
dc.identifier.otherPubMed: 41410161
dc.identifier.otherWOS: 001651771900010
dc.identifier.urihttp://hdl.handle.net/10362/199062
dc.identifier.urlhttps://www.scopus.com/pages/publications/105025171186
dc.language.isoeng
dc.peerreviewedyes
dc.subjectantigen-specific Treg
dc.subjectcGVHD
dc.subjectHLA class II
dc.subjectHLA-matched
dc.subjectmHA
dc.subjectImmunology and Allergy
dc.subjectImmunology
dc.titleSelection and Characterisation of Minor Histocompatibility Antigen-Specific Regulatory T Cells in Fully HLA-Matched Setting for GVHD Therapyen
dc.typejournal article
degois.publication.issue12
degois.publication.titleEuropean Journal of Immunology
degois.publication.volume55
dspace.entity.typePublication
rcaap.rightsopenAccess

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