Successful in vitro priming of EBV-specific CD8+ T cells endowed with strong cytotoxic function from T cells of EBV-seronegative children

P. Comoli, F. Ginevri, R. Maccario, C. Frasson, U. Valente, S. Basso, M. Labirio, G. C. Huang, E. Verrina, F. Baldanti, F. Perfumo, F. Locatelli

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV)-seronegative transplant recipients are at high risk of developing EBV-associated post-transplant lymphoproliferative disorder (PTLD), and would maximally benefit from an EBV-directed T-cell therapy for prevention or treatment of PTLD. So far, efforts to activate CD8+ EBV-specific cytotoxic T lymphocytes (CTL) endowed with high specific cytotoxicity from EBV-seronegative children have failed. We compared the CD8+ CTL priming efficiency of three different modified activation protocols, based on lymphoblastoid cell lines (LCL) stimulation potentially enhanced by either LCL presentation through dendritic cells, or selection of IFN-γ+ cultured cells, or culture in the presence of rhIL-12 and rhIL-7, according to the standard protocol for reactivation of EBV-specific CTL. We found that only specific LCL stimulation in the presence of rhIL-12 and rhIL-7 was able to reproducibly expand EBV-specific CD8+ CTL endowed with strong cytotoxic activity from truly EBV-seronegative children. The lines thus activated, which included specificities toward EBV latent and lytic proteins, showed high percentage CD8+ T cells, with

Original languageEnglish
Pages (from-to)2169-2176
Number of pages8
JournalAmerican Journal of Transplantation
Volume6
Issue number9
DOIs
Publication statusPublished - Sep 2006

Fingerprint

Human Herpesvirus 4
T-Lymphocytes
Cytotoxic T-Lymphocytes
Lymphoproliferative Disorders
Cell Line
Transplants
In Vitro Techniques
Cell- and Tissue-Based Therapy
Dendritic Cells
Cultured Cells
Cell Culture Techniques

Keywords

  • CD8+ T-cell priming
  • Cytotoxic T lymphocytes
  • Epstein-Barr virus
  • Pediatric transplantation
  • Post-transplant lymphoproliferative disorder

ASJC Scopus subject areas

  • Immunology

Cite this

Successful in vitro priming of EBV-specific CD8+ T cells endowed with strong cytotoxic function from T cells of EBV-seronegative children. / Comoli, P.; Ginevri, F.; Maccario, R.; Frasson, C.; Valente, U.; Basso, S.; Labirio, M.; Huang, G. C.; Verrina, E.; Baldanti, F.; Perfumo, F.; Locatelli, F.

In: American Journal of Transplantation, Vol. 6, No. 9, 09.2006, p. 2169-2176.

Research output: Contribution to journalArticle

@article{95a81b6a97384de6b64597dd8c56cdf8,
title = "Successful in vitro priming of EBV-specific CD8+ T cells endowed with strong cytotoxic function from T cells of EBV-seronegative children",
abstract = "Epstein-Barr virus (EBV)-seronegative transplant recipients are at high risk of developing EBV-associated post-transplant lymphoproliferative disorder (PTLD), and would maximally benefit from an EBV-directed T-cell therapy for prevention or treatment of PTLD. So far, efforts to activate CD8+ EBV-specific cytotoxic T lymphocytes (CTL) endowed with high specific cytotoxicity from EBV-seronegative children have failed. We compared the CD8+ CTL priming efficiency of three different modified activation protocols, based on lymphoblastoid cell lines (LCL) stimulation potentially enhanced by either LCL presentation through dendritic cells, or selection of IFN-γ+ cultured cells, or culture in the presence of rhIL-12 and rhIL-7, according to the standard protocol for reactivation of EBV-specific CTL. We found that only specific LCL stimulation in the presence of rhIL-12 and rhIL-7 was able to reproducibly expand EBV-specific CD8+ CTL endowed with strong cytotoxic activity from truly EBV-seronegative children. The lines thus activated, which included specificities toward EBV latent and lytic proteins, showed high percentage CD8+ T cells, with",
keywords = "CD8+ T-cell priming, Cytotoxic T lymphocytes, Epstein-Barr virus, Pediatric transplantation, Post-transplant lymphoproliferative disorder",
author = "P. Comoli and F. Ginevri and R. Maccario and C. Frasson and U. Valente and S. Basso and M. Labirio and Huang, {G. C.} and E. Verrina and F. Baldanti and F. Perfumo and F. Locatelli",
year = "2006",
month = "9",
doi = "10.1111/j.1600-6143.2006.01429.x",
language = "English",
volume = "6",
pages = "2169--2176",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Successful in vitro priming of EBV-specific CD8+ T cells endowed with strong cytotoxic function from T cells of EBV-seronegative children

AU - Comoli, P.

AU - Ginevri, F.

AU - Maccario, R.

AU - Frasson, C.

AU - Valente, U.

AU - Basso, S.

AU - Labirio, M.

AU - Huang, G. C.

AU - Verrina, E.

AU - Baldanti, F.

AU - Perfumo, F.

AU - Locatelli, F.

PY - 2006/9

Y1 - 2006/9

N2 - Epstein-Barr virus (EBV)-seronegative transplant recipients are at high risk of developing EBV-associated post-transplant lymphoproliferative disorder (PTLD), and would maximally benefit from an EBV-directed T-cell therapy for prevention or treatment of PTLD. So far, efforts to activate CD8+ EBV-specific cytotoxic T lymphocytes (CTL) endowed with high specific cytotoxicity from EBV-seronegative children have failed. We compared the CD8+ CTL priming efficiency of three different modified activation protocols, based on lymphoblastoid cell lines (LCL) stimulation potentially enhanced by either LCL presentation through dendritic cells, or selection of IFN-γ+ cultured cells, or culture in the presence of rhIL-12 and rhIL-7, according to the standard protocol for reactivation of EBV-specific CTL. We found that only specific LCL stimulation in the presence of rhIL-12 and rhIL-7 was able to reproducibly expand EBV-specific CD8+ CTL endowed with strong cytotoxic activity from truly EBV-seronegative children. The lines thus activated, which included specificities toward EBV latent and lytic proteins, showed high percentage CD8+ T cells, with

AB - Epstein-Barr virus (EBV)-seronegative transplant recipients are at high risk of developing EBV-associated post-transplant lymphoproliferative disorder (PTLD), and would maximally benefit from an EBV-directed T-cell therapy for prevention or treatment of PTLD. So far, efforts to activate CD8+ EBV-specific cytotoxic T lymphocytes (CTL) endowed with high specific cytotoxicity from EBV-seronegative children have failed. We compared the CD8+ CTL priming efficiency of three different modified activation protocols, based on lymphoblastoid cell lines (LCL) stimulation potentially enhanced by either LCL presentation through dendritic cells, or selection of IFN-γ+ cultured cells, or culture in the presence of rhIL-12 and rhIL-7, according to the standard protocol for reactivation of EBV-specific CTL. We found that only specific LCL stimulation in the presence of rhIL-12 and rhIL-7 was able to reproducibly expand EBV-specific CD8+ CTL endowed with strong cytotoxic activity from truly EBV-seronegative children. The lines thus activated, which included specificities toward EBV latent and lytic proteins, showed high percentage CD8+ T cells, with

KW - CD8+ T-cell priming

KW - Cytotoxic T lymphocytes

KW - Epstein-Barr virus

KW - Pediatric transplantation

KW - Post-transplant lymphoproliferative disorder

UR - http://www.scopus.com/inward/record.url?scp=33746909113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746909113&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2006.01429.x

DO - 10.1111/j.1600-6143.2006.01429.x

M3 - Article

C2 - 16796723

AN - SCOPUS:33746909113

VL - 6

SP - 2169

EP - 2176

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 9

ER -