A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy.
J Immunol
; 183(4): 2837-50, 2009 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-19635907
ABSTRACT
Adoptive transfer of virus-specific T cells can treat infections complicating allogeneic hematopoietic cell transplants. However, autologous APCs are often limited in supply. In this study, we describe a panel of artificial APCs (AAPCs) consisting of murine 3T3 cells transduced to express human B7.1, ICAM-1, and LFA-3 that each stably express one of a series of six common HLA class I alleles. In comparative analyses, T cells sensitized with AAPCs expressing a shared HLA allele or autologous APCs loaded with a pool of 15-mer spanning the sequence of CMVpp65 produced similar yields of HLA-restricted CMVpp65-specific T cells; significantly higher yields could be achieved by sensitization with AAPCs transduced to express the CMVpp65 protein. T cells generated were CD8(+), IFN-gamma(+), and exhibited HLA-restricted CMVpp65-specific cytotoxicity. T cells sensitized with either peptide-loaded or transduced AAPCs recognized epitopes presented by each HLA allele known to be immunogenic in humans. Sensitization with AAPCs also permitted expansion of IFN-gamma(+) cytotoxic effector cells against subdominant epitopes that were either absent or in low frequencies in T cells sensitized with autologous APCs. This replenishable panel of AAPCs can be used for immediate sensitization and expansion of virus-specific T cells of desired HLA restriction for adoptive immunotherapy. It may be of particular value for recipients of transplants from HLA-disparate donors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Ativação Linfocitária
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Linfócitos T Citotóxicos
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Antígenos de Histocompatibilidade Classe I
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Proteínas da Matriz Viral
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Epitopos Imunodominantes
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Imunoterapia Adotiva
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Citomegalovirus
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Alelos
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos