Human parainfluenza virus-3 can be targeted by rapidly ex vivo expanded T lymphocytes.
Cytotherapy
; 18(12): 1515-1524, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27692559
ABSTRACT
BACKGROUND AIMS:
Human parainfluenza virus-3 (HPIV) is a common cause of respiratory infection in immunocompromised patients and currently has no effective therapies. Virus-specific T-cell therapy has been successful for the treatment or prevention of viral infections in immunocompromised patients but requires determination of T-cell antigens on targeted viruses.METHODS:
HPIV3-specific T cells were expanded from peripheral blood of healthy donors using a rapid generation protocol targeting four HPIV3 proteins. Immunophenotyping was performed by flow cytometry. Viral specificity was determined by interferon (IFN)-γ ELISpot, intracellular cytokine staining and cytokine measurements from culture supernatants by Luminex assay. Cytotoxic activity was tested by 51Cr release and CD107a mobilization assays. Virus-specific T cells targeting six viruses were then produced by rapid protocol, and the phenotype of HPIV3-specific T cells was determined by immunomagnetic sorting for IFN-γ-producing cells.RESULTS:
HPIV3-specific T cells were expanded from 13 healthy donors. HPIV3-specific T cells showed a CD4+ predominance (mean CD4CD8 ratio 2.89) and demonstrated specificity for multiple HPIV3 antigens. The expanded T cells were polyfunctional based on cytokine production but only had a minor cytotoxic component. T cells targeting six viruses in a single product similarly showed HPIV3 specificity, with a predominant effector memory phenotype (CD3+/CD45RA-/CCR7-) in responder cells.DISCUSSION:
HPIV3-specific T cells can be produced using a rapid ex vivo protocol from healthy donors and are predominantly CD4+ T cells with Th1 activity. HPIV3 epitopes can also be successfully targeted alongside multiple other viral epitopes in production of six-virus T cells, without loss of HPIV3 specificity. These products may be clinically beneficial to combat HPIV3 infections by adoptive T-cell therapy in immune-compromised patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por Respirovirus
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Linfócitos T CD4-Positivos
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Vírus da Parainfluenza 3 Humana
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Linfócitos T CD8-Positivos
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Terapia Baseada em Transplante de Células e Tecidos
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Antígenos Virais
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
Cytotherapy
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos