Generation of cytomegalovirus (CMV)-specific CD4 T cell lines devoid of alloreactivity, by use of a mixture of CMV-phosphoprotein 65 peptides for reconstitution of the T helper repertoire

Giuseppina Li Pira, Laura Bottone, Federico Ivaldi, Augusto Tagliamacco, Stefano Fiordoro, Annamaria Ricciardi, Giancarlo Barbano, Fabrizio Manca

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background. CD8 cells specific for cytomegalovirus (CMV) provide valuable support in immunocompromised patients. Recent studies have focused on the generation of cytotoxic T lymphocyte (CTL) lines by use of new biotechnological techniques. Yet CD4 cells have been neglected, even though they contribute to the persistence of adoptively transferred CTLs. Methods. We identified novel T helper (Th) peptides recognized by CD4 cells on the immunodominant protein pp65. These peptides were used as a mixture to generate CD4 cell lines. Results. The peptide library, which, theoretically, is recognized by 85% of white individuals on the basis of the frequency of the relevant human leukocyte antigen class II alleles, was stimulatory for 82% of pp65 responders. T cell lines generated by use of the pool recognized protein antigens. Selection for CMV-specific cells resulted in rapid depletion of allospecific T cells. Selection with individual peptides allowed further selection against potential cross-alloreactivity. Cultured CD4 cells showed no signs of functional senescence. CD4 cells activated by use of a Th peptide helped expand CMV-specific CTLs. Conclusions. By use of a simple procedure, an immunodominant peptide library can generate T cell lines from allodonors, for the perspective reconstitution of the Th repertoire in immunocompromised hemopoietic stem-cell transplant recipients.

Original languageEnglish
Pages (from-to)215-226
Number of pages12
JournalJournal of Infectious Diseases
Volume191
Issue number2
DOIs
Publication statusPublished - Jan 15 2005

Fingerprint

Peptide T
Cytomegalovirus
T-Lymphocytes
Cell Line
Peptide Library
Peptides
Immunocompromised Host
Cytotoxic T-Lymphocytes
HLA Antigens
Cultured Cells
Proteins
Stem Cells
Alleles
cytomegalovirus matrix protein 65kDa
Transplants
Antigens

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Generation of cytomegalovirus (CMV)-specific CD4 T cell lines devoid of alloreactivity, by use of a mixture of CMV-phosphoprotein 65 peptides for reconstitution of the T helper repertoire. / Li Pira, Giuseppina; Bottone, Laura; Ivaldi, Federico; Tagliamacco, Augusto; Fiordoro, Stefano; Ricciardi, Annamaria; Barbano, Giancarlo; Manca, Fabrizio.

In: Journal of Infectious Diseases, Vol. 191, No. 2, 15.01.2005, p. 215-226.

Research output: Contribution to journalArticle

@article{b3eb28e22e654ef9bc3379b1473a0d84,
title = "Generation of cytomegalovirus (CMV)-specific CD4 T cell lines devoid of alloreactivity, by use of a mixture of CMV-phosphoprotein 65 peptides for reconstitution of the T helper repertoire",
abstract = "Background. CD8 cells specific for cytomegalovirus (CMV) provide valuable support in immunocompromised patients. Recent studies have focused on the generation of cytotoxic T lymphocyte (CTL) lines by use of new biotechnological techniques. Yet CD4 cells have been neglected, even though they contribute to the persistence of adoptively transferred CTLs. Methods. We identified novel T helper (Th) peptides recognized by CD4 cells on the immunodominant protein pp65. These peptides were used as a mixture to generate CD4 cell lines. Results. The peptide library, which, theoretically, is recognized by 85{\%} of white individuals on the basis of the frequency of the relevant human leukocyte antigen class II alleles, was stimulatory for 82{\%} of pp65 responders. T cell lines generated by use of the pool recognized protein antigens. Selection for CMV-specific cells resulted in rapid depletion of allospecific T cells. Selection with individual peptides allowed further selection against potential cross-alloreactivity. Cultured CD4 cells showed no signs of functional senescence. CD4 cells activated by use of a Th peptide helped expand CMV-specific CTLs. Conclusions. By use of a simple procedure, an immunodominant peptide library can generate T cell lines from allodonors, for the perspective reconstitution of the Th repertoire in immunocompromised hemopoietic stem-cell transplant recipients.",
author = "{Li Pira}, Giuseppina and Laura Bottone and Federico Ivaldi and Augusto Tagliamacco and Stefano Fiordoro and Annamaria Ricciardi and Giancarlo Barbano and Fabrizio Manca",
year = "2005",
month = "1",
day = "15",
doi = "10.1086/427040",
language = "English",
volume = "191",
pages = "215--226",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Generation of cytomegalovirus (CMV)-specific CD4 T cell lines devoid of alloreactivity, by use of a mixture of CMV-phosphoprotein 65 peptides for reconstitution of the T helper repertoire

AU - Li Pira, Giuseppina

AU - Bottone, Laura

AU - Ivaldi, Federico

AU - Tagliamacco, Augusto

AU - Fiordoro, Stefano

AU - Ricciardi, Annamaria

AU - Barbano, Giancarlo

AU - Manca, Fabrizio

PY - 2005/1/15

Y1 - 2005/1/15

N2 - Background. CD8 cells specific for cytomegalovirus (CMV) provide valuable support in immunocompromised patients. Recent studies have focused on the generation of cytotoxic T lymphocyte (CTL) lines by use of new biotechnological techniques. Yet CD4 cells have been neglected, even though they contribute to the persistence of adoptively transferred CTLs. Methods. We identified novel T helper (Th) peptides recognized by CD4 cells on the immunodominant protein pp65. These peptides were used as a mixture to generate CD4 cell lines. Results. The peptide library, which, theoretically, is recognized by 85% of white individuals on the basis of the frequency of the relevant human leukocyte antigen class II alleles, was stimulatory for 82% of pp65 responders. T cell lines generated by use of the pool recognized protein antigens. Selection for CMV-specific cells resulted in rapid depletion of allospecific T cells. Selection with individual peptides allowed further selection against potential cross-alloreactivity. Cultured CD4 cells showed no signs of functional senescence. CD4 cells activated by use of a Th peptide helped expand CMV-specific CTLs. Conclusions. By use of a simple procedure, an immunodominant peptide library can generate T cell lines from allodonors, for the perspective reconstitution of the Th repertoire in immunocompromised hemopoietic stem-cell transplant recipients.

AB - Background. CD8 cells specific for cytomegalovirus (CMV) provide valuable support in immunocompromised patients. Recent studies have focused on the generation of cytotoxic T lymphocyte (CTL) lines by use of new biotechnological techniques. Yet CD4 cells have been neglected, even though they contribute to the persistence of adoptively transferred CTLs. Methods. We identified novel T helper (Th) peptides recognized by CD4 cells on the immunodominant protein pp65. These peptides were used as a mixture to generate CD4 cell lines. Results. The peptide library, which, theoretically, is recognized by 85% of white individuals on the basis of the frequency of the relevant human leukocyte antigen class II alleles, was stimulatory for 82% of pp65 responders. T cell lines generated by use of the pool recognized protein antigens. Selection for CMV-specific cells resulted in rapid depletion of allospecific T cells. Selection with individual peptides allowed further selection against potential cross-alloreactivity. Cultured CD4 cells showed no signs of functional senescence. CD4 cells activated by use of a Th peptide helped expand CMV-specific CTLs. Conclusions. By use of a simple procedure, an immunodominant peptide library can generate T cell lines from allodonors, for the perspective reconstitution of the Th repertoire in immunocompromised hemopoietic stem-cell transplant recipients.

UR - http://www.scopus.com/inward/record.url?scp=11844258837&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11844258837&partnerID=8YFLogxK

U2 - 10.1086/427040

DO - 10.1086/427040

M3 - Article

VL - 191

SP - 215

EP - 226

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 2

ER -