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Article: Human CD8+ Regulatory T Cells Inhibit GVHD and Preserve General Immunity in Humanized Mice

TitleHuman CD8+ Regulatory T Cells Inhibit GVHD and Preserve General Immunity in Humanized Mice
Authors
Issue Date2013
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://www.sciencemag.org/marketing/stm/
Citation
Science Translational Medicine, 2013, v. 5 n. 168, p. 168ra9 How to Cite?
AbstractGraft-versus-host disease (GVHD) is a lethal complication of allogeneic bone marrow transplantation (BMT). Immunosuppressive agents are currently used to control GVHD but may cause general immune suppression and limit the effectiveness of BMT. Adoptive transfer of regulatory T cells (T(regs)) can prevent GVHD in rodents, suggesting a therapeutic potential of T(regs) for GVHD in humans. However, the clinical application of T(reg)-based therapy is hampered by the low frequency of human T(regs) and the lack of a reliable model to test their therapeutic effects in vivo. Recently, we successfully generated human alloantigen-specific CD8(hi) T(regs) in a large scale from antigenically naive precursors ex vivo using allogeneic CD40-activated B cells as stimulators. We report a human allogeneic GVHD model established in humanized mice to mimic GVHD after BMT in humans. We demonstrate that ex vivo-induced CD8(hi) T(regs) controlled GVHD in an allospecific manner by reducing alloreactive T cell proliferation as well as decreasing inflammatory cytokine and chemokine secretion within target organs through a CTLA-4-dependent mechanism in humanized mice. These CD8(hi) T(regs) induced long-term tolerance effectively without compromising general immunity and graft-versus-tumor activity. Our results support testing of human CD8(hi) T(regs) in GVHD in clinical trials.
Persistent Identifierhttp://hdl.handle.net/10722/191464
ISSN
2015 SCImago Journal Rankings: 8.931
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZheng, Jen_US
dc.contributor.authorLiu, Yen_US
dc.contributor.authorLiu, Yen_US
dc.contributor.authorLiu, Men_US
dc.contributor.authorXiang, Zen_US
dc.contributor.authorLam, KT-
dc.contributor.authorLewis, DB-
dc.contributor.authorLau, YL-
dc.contributor.authorTu, W-
dc.date.accessioned2013-10-15T07:01:24Z-
dc.date.available2013-10-15T07:01:24Z-
dc.date.issued2013en_US
dc.identifier.citationScience Translational Medicine, 2013, v. 5 n. 168, p. 168ra9en_US
dc.identifier.issn1946-6242-
dc.identifier.urihttp://hdl.handle.net/10722/191464-
dc.description.abstractGraft-versus-host disease (GVHD) is a lethal complication of allogeneic bone marrow transplantation (BMT). Immunosuppressive agents are currently used to control GVHD but may cause general immune suppression and limit the effectiveness of BMT. Adoptive transfer of regulatory T cells (T(regs)) can prevent GVHD in rodents, suggesting a therapeutic potential of T(regs) for GVHD in humans. However, the clinical application of T(reg)-based therapy is hampered by the low frequency of human T(regs) and the lack of a reliable model to test their therapeutic effects in vivo. Recently, we successfully generated human alloantigen-specific CD8(hi) T(regs) in a large scale from antigenically naive precursors ex vivo using allogeneic CD40-activated B cells as stimulators. We report a human allogeneic GVHD model established in humanized mice to mimic GVHD after BMT in humans. We demonstrate that ex vivo-induced CD8(hi) T(regs) controlled GVHD in an allospecific manner by reducing alloreactive T cell proliferation as well as decreasing inflammatory cytokine and chemokine secretion within target organs through a CTLA-4-dependent mechanism in humanized mice. These CD8(hi) T(regs) induced long-term tolerance effectively without compromising general immunity and graft-versus-tumor activity. Our results support testing of human CD8(hi) T(regs) in GVHD in clinical trials.-
dc.languageengen_US
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://www.sciencemag.org/marketing/stm/-
dc.relation.ispartofScience Translational Medicineen_US
dc.rightsScience Translational Medicine. Copyright © American Association for the Advancement of Science.-
dc.subject.meshCD8-Positive T-Lymphocytes - immunology - pathology - secretion-
dc.subject.meshGraft vs Host Disease - immunology - pathology - prevention and control-
dc.subject.meshImmunity - immunology-
dc.subject.meshLymphocyte Activation - immunology-
dc.subject.meshT-Lymphocytes, Regulatory - immunology - pathology - secretion-
dc.titleHuman CD8+ Regulatory T Cells Inhibit GVHD and Preserve General Immunity in Humanized Miceen_US
dc.typeArticleen_US
dc.identifier.emailZheng, J: teddy629@hku.hken_US
dc.identifier.emailLiu, Y: yinpingl@hku.hken_US
dc.identifier.emailLiu, Y: lyuany@hku.hken_US
dc.identifier.emailLam, KT: ktlama@graduate.hku.hken_US
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.emailTu, W: wwtu@hku.hk-
dc.identifier.authorityLiu, Y=rp00269en_US
dc.identifier.authorityLau, YL=rp00361en_US
dc.identifier.authorityTu, W=rp00416en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/scitranslmed.3004943-
dc.identifier.pmid23325802-
dc.identifier.hkuros227396en_US
dc.identifier.hkuros225530-
dc.identifier.hkuros221467-
dc.identifier.volume5-
dc.identifier.issue168-
dc.identifier.spage168ra9-
dc.identifier.epage168ra9-
dc.identifier.isiWOS:000313739200006-
dc.publisher.placeUnited States-

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