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 language | English |
|---|---|
| Pages (from-to) | 215-226 |
| Number of pages | 12 |
| Journal | Journal of Infectious Diseases |
| Volume | 191 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 15 2005 |
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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 journal › Article
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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.
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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 -