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

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

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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