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2.
Ann N Y Acad Sci ; 1062: 104-15, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16461793

RESUMO

Human adenoviruses are ubiquitous lytic DNA viruses that can be divided into 51 different serotypes, grouped from A to F on the basis of genome size, composition, homology, and organization. Adenovirus infections, although frequent, are rarely fatal in immunocompetent individuals, due to potent innate and adaptive immune responses. By contrast, adenoviruses are a significant cause of morbidity and mortality in immunosuppressed individuals, for whom there are limited treatment options. Since antiviral drugs have variable efficacy in the treatment of severe adenovirus disease, iatrogenic reconstitution with in vitro expanded virus-specific cytotoxic T lymphocytes (CTLs) is an attractive option for prophylaxis and treatment, particularly because the endogenous recovery of adenovirus-specific T cells has proved important in controlling infection in vivo. Thus, we have characterized human T-cell responses to adenovirus in vitro and explored the potential of adoptive T-cell immunotherapy as a prophylactic or therapeutic strategy for adenovirus infections posttransplant.


Assuntos
Infecções por Adenoviridae/imunologia , Infecções por Adenoviridae/terapia , Transferência Adotiva/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos T/transplante , Linfócitos T/virologia , Infecções por Adenoviridae/mortalidade , Sequência de Aminoácidos , Humanos , Dados de Sequência Molecular , Linfócitos T/imunologia
3.
Cytotherapy ; 5(3): 231-40, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12850791

RESUMO

BACKGROUND: EBV-associated malignancies with a Type II latency gene expression pattern, such as EBV-positive HD, or nasopharyngeal carcinoma, frequently express the EBV latency Ag LMP2a. Hence, they provide a potential target for adoptive immunotherapy using in vitro-generated LMP2a-specific cytotoxic T lymphocytes (CTL). In this study, LMP2a-specific CTL were specifically amplified and the influence of rIL12 and rIL15 on the culture outcome was tested. METHODS: PBMC from donors were stimulated twice with autologous DC transduced with an adenovirus vector expressing LMP2a. This led to a significant expansion of LMP2a-tetramer-specific CTL, which were subsequently further expanded with autologous EBV-transformed B-lymphoblastoid cells (LCL). The addition of rIL12 and rIL15 to the standard IL2-containing culture medium enhanced the proliferation of LMP2a-specific CTL. RESULTS: While rIL15 did not change the pattern of cytokines secreted by LMP2a-CTL, rIL12 enhanced the production of Th1/Tc1 cytokines, such as IFN-n, while suppressing the production of the Th2/Tc2 cytokine IL5. DISCUSSION: Stimulation of CTL cultures with rIL12 or rIL15 will generate CTL more rapidly, facilitating the application of this approach for patients with these EBV-associated disorders.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Interleucina-12/farmacologia , Interleucina-15/farmacologia , Linfócitos T Citotóxicos/imunologia , Proteínas da Matriz Viral/imunologia , Adenoviridae/genética , Linhagem Celular , Citocinas/metabolismo , Células Dendríticas/imunologia , Infecções por Vírus Epstein-Barr/terapia , Vetores Genéticos , Humanos , Imunoterapia Adotiva , Interleucina-12/genética , Interleucina-15/genética , Leucócitos Mononucleares/imunologia , Ativação Linfocitária , Proteínas Recombinantes/farmacologia , Linfócitos T Citotóxicos/transplante , Proteínas da Matriz Viral/genética
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