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
Identifieur interne : 000A49 ( Istex/Checkpoint ); précédent : 000A48; suivant : 000A50Generation 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
Auteurs : Giuseppina Li Pira ; Laura Bottone [Italie] ; Federico Ivaldi ; Augusto Tagliamacco ; Stefano Fiordoro ; Annamaria Ricciardi ; Giancarlo Barbano ; Fabrizio Manca [Italie]Source :
- Journal of Infectious Diseases [ 0022-1899 ] ; 2005.
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.
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DOI: 10.1086/427040
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<front><div type="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.</div>
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