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Article: Acceleration of apoptosis in CD4+CD8+ thymocytes by rapamycin accompanied by increased CD4+CD25+ T cells in the periphery

TitleAcceleration of apoptosis in CD4+CD8+ thymocytes by rapamycin accompanied by increased CD4+CD25+ T cells in the periphery
Authors
Issue Date2004
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.com
Citation
Transplantation, 2004, v. 77 n. 2, p. 183-189 How to Cite?
AbstractBackground. Rapamycin (Rapa) is an immunosuppressant that is used in patients and animal models to control allograft rejection. Its mechanisms of action are not fully understood. In this article, the authors have investigated the effects of therapeutic doses of Rapa on both thymic and peripheral T-cell populations in the adult rat. Methods. The therapeutic dosage of Rapa was optimized using cardiac transplantation between LEW and DA rats. Thymic morphology was assessed by hematoxylin-eosin staining. Flow cytometric analysis was performed to analyze T-cell phenotype and apoptosis. T-cell receptor (TCR)-mediated T-cell responsiveness was evaluated by 3[H]-thymidine deoxyribose incorporation. Results. Rapa induced atrophy in the thymus but not in peripheral lymphoid organs. Moreover, fibrosis occurred in thymus that was long-lasting after Rapa withdrawal. In animals treated with Rapa, there was a significant reduction in CD4+CD8+ thymocytes caused by accelerated apoptosis, whereas CD4-CD8-, CD4 +CD8-, and CD8+CD4- populations remained unaffected. In contrast, the cellularity of the periphery lymphoid organs was not altered. Within the CD4+ thymocyte population, CD4+CD25+ thymocytes were resistant to Rapa-accelerated apoptosis, and in the periphery, the ratio of CD4+CD25+ to CD4+CD25- T cells was increased. Notably, the peripheral CD4+CD25+ T cells were hyporesponsive to TCR-mediated activation. Conclusions. The resistance of the peripheral CD4 +CD25+ T cells to Rapa treatment might contribute to its immunosuppressive action. The long-term effects of Rapa on thymus atrophy and thymocyte development requires consideration with respect to its clinical application.
Persistent Identifierhttp://hdl.handle.net/10722/88405
ISSN
2015 Impact Factor: 3.69
2015 SCImago Journal Rankings: 1.699
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTian, Len_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorYuan, Zen_HK
dc.contributor.authorLamb, JRen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T09:42:56Z-
dc.date.available2010-09-06T09:42:56Z-
dc.date.issued2004en_HK
dc.identifier.citationTransplantation, 2004, v. 77 n. 2, p. 183-189en_HK
dc.identifier.issn0041-1337en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88405-
dc.description.abstractBackground. Rapamycin (Rapa) is an immunosuppressant that is used in patients and animal models to control allograft rejection. Its mechanisms of action are not fully understood. In this article, the authors have investigated the effects of therapeutic doses of Rapa on both thymic and peripheral T-cell populations in the adult rat. Methods. The therapeutic dosage of Rapa was optimized using cardiac transplantation between LEW and DA rats. Thymic morphology was assessed by hematoxylin-eosin staining. Flow cytometric analysis was performed to analyze T-cell phenotype and apoptosis. T-cell receptor (TCR)-mediated T-cell responsiveness was evaluated by 3[H]-thymidine deoxyribose incorporation. Results. Rapa induced atrophy in the thymus but not in peripheral lymphoid organs. Moreover, fibrosis occurred in thymus that was long-lasting after Rapa withdrawal. In animals treated with Rapa, there was a significant reduction in CD4+CD8+ thymocytes caused by accelerated apoptosis, whereas CD4-CD8-, CD4 +CD8-, and CD8+CD4- populations remained unaffected. In contrast, the cellularity of the periphery lymphoid organs was not altered. Within the CD4+ thymocyte population, CD4+CD25+ thymocytes were resistant to Rapa-accelerated apoptosis, and in the periphery, the ratio of CD4+CD25+ to CD4+CD25- T cells was increased. Notably, the peripheral CD4+CD25+ T cells were hyporesponsive to TCR-mediated activation. Conclusions. The resistance of the peripheral CD4 +CD25+ T cells to Rapa treatment might contribute to its immunosuppressive action. The long-term effects of Rapa on thymus atrophy and thymocyte development requires consideration with respect to its clinical application.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.comen_HK
dc.relation.ispartofTransplantationen_HK
dc.rightsTransplantation. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosis - immunologyen_HK
dc.subject.meshAtrophyen_HK
dc.subject.meshCD4-Positive T-Lymphocytes - drug effects - immunologyen_HK
dc.subject.meshCD8-Positive T-Lymphocytes - drug effects - immunologyen_HK
dc.subject.meshHeart Transplantation - immunologyen_HK
dc.subject.meshImmunosuppressive Agents - pharmacologyen_HK
dc.subject.meshLymphocyte Activation - drug effectsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshModels, Animalen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Inbred Lewen_HK
dc.subject.meshReceptors, Interleukin-2 - blooden_HK
dc.subject.meshSirolimus - pharmacologyen_HK
dc.subject.meshT-Lymphocyte Subsets - immunologyen_HK
dc.subject.meshT-Lymphocytes - immunologyen_HK
dc.subject.meshThymus Gland - drug effects - immunology - pathologyen_HK
dc.subject.meshTransplantation, Homologous - immunologyen_HK
dc.titleAcceleration of apoptosis in CD4+CD8+ thymocytes by rapamycin accompanied by increased CD4+CD25+ T cells in the peripheryen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0041-1337&volume=77&issue=2&spage=183&epage=189&date=2004&atitle=Acceleration+of+apoptosis+in+CD4+CD8++thymocytes+by+rapamycin+accompanied+by+increased+CD4+CD25++T+cells+in+the+peripheryen_HK
dc.identifier.emailLu, L:liweilu@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH:paultam@hkucc.hku.hken_HK
dc.identifier.authorityLu, L=rp00477en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/01.TP.0000101005.44661.3Een_HK
dc.identifier.pmid14742978-
dc.identifier.scopuseid_2-s2.0-0742322207en_HK
dc.identifier.hkuros85941en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0742322207&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume77en_HK
dc.identifier.issue2en_HK
dc.identifier.spage183en_HK
dc.identifier.epage189en_HK
dc.identifier.isiWOS:000188705400003-
dc.publisher.placeUnited Statesen_HK

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