Lymphodepletion by short-term chemotherapy does not alter the highly stable and persistent EBV specific CD8 T cell repertoire

Détails

ID Serval
serval:BIB_592B1B176E97
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
Lymphodepletion by short-term chemotherapy does not alter the highly stable and persistent EBV specific CD8 T cell repertoire
Titre de la conférence
Annual Congress SGAI-SSAI, Advances in immunology and allergology: from research to diagnosis and therapy
Auteur⸱e⸱s
Iancu E.M., Laurent J., Wieckowski S., Gupta B., Leyvraz S., Meylan P., Romero P., Michelin O., Speiser D., Rufer N.
Adresse
Lugano, Switzerland, March 17-18, 2011
ISBN
0344-5062
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
34
Série
Allergologie
Pages
101-102
Langue
anglais
Notes
Meeting Abstract
Résumé
Protective T cell responses againstpersistent viruses like Epstein-Barrvirus in healthy individuals are characterizedby a remarkable stability ofthe T cell receptor (TCR) clonotypicrepertoire, with highly preservedclonotype selection and persistenceover time. Here, we extended recentwork to the study of EBV-specificCD8 T cell responses in melanomapatients treated by short-term chemotherapyfor transient lymphodepletion,followed by adoptive cell transfer(ACT) and immune reconstitutionfor cancer therapy. After this treatment,we observed increased proportionsof virus-specific T cells in 3/5patients, accompanied by a more differentiatedphenotype (EMRA/CD28neg), compared to specific cells ofhealthy individuals. Yet, similarly tohealthy donors, clonotype selectionand composition of virus-specific Tcells varied along the pathway of celldifferentiation, with some clonotypesthat were selected with late differentiation,while others were not. Aftertreatment, we did not observe noveldominant clonotypes, likely related toabsence of EBV reactivation measuredas viral load levels by quantitativePCR in PBMCs and antibody levelsin plasma samples. Furthermore,public TCR BV signatures were frequentlyfound within T cell clonotypesthat dominated the repertoiresof patients, in line with those observedin healthy individuals. Ourfindings indicate that even in situationswhere the immune system isstrongly challenged such as followinglymphodepletion and homeostatic repopulation,cytotoxic T cells specificfor EBV remain strikingly stable interms of clonotype selection and com-position along T cell differentiation.We are currently characterizing theclonotype selection and gene expressionprofiles of single EBV-specificCD8 T lymphocytes sorted ex-vivo inone patient who underwent two cyclesof lymphodepletion with escaladingdoses of chemotherapy overone-year interval. Observations madefrom this setting will provide additionalinsight into the degree of stabilityof virus specific T cells, and changesin the expression levels of genesimportant for cytolytic function andlong-term survival of T cells. Thiswork is supported by the Swiss NationalCenter of Competence in Research(NCCR) Molecular Oncology,and the Swiss National Science Foundation.
Web of science
Création de la notice
29/03/2011 13:33
Dernière modification de la notice
20/08/2019 14:12
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