CD8 T cell priming in the presence of IFN-α renders CTLs with improved responsiveness to homeostatic cytokines and recall antigens: important traits for adoptive T cell therapy.
J Immunol
; 189(7): 3299-310, 2012 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-22925929
ABSTRACT
Previous mouse and human studies have demonstrated that direct IFN-α/ß signaling on naive CD8 T cells is critical to support their expansion and acquisition of effector functions. In this study, we show that human naive CD8 T cells primed in the presence of IFN-α possess a heightened ability to respond to homeostatic cytokines and to secondary Ag stimulation, but rather than differentiating to effector or memory CTLs, they preserve nature-like phenotypic features. These are qualities associated with greater efficacy in adoptive immunotherapy. In a mouse model of adoptive transfer, CD8 T cells primed in the presence of IFN-α are able to persist and to mediate a robust recall response even after a long period of naturally driven homeostatic maintenance. The long-lasting persistence of IFN-α-primed CD8 T cells is favored by their enhanced responsiveness to IL-15 and IL-7, as demonstrated in IL-15(-/-) and IL-7(-/-) recipient mice. In humans, exposure to IFN-α during in vitro priming of naive HLA-A2(+) CD8 T cells with autologous dendritic cells loaded with MART1(26-35) peptide renders CD8 T cells with an improved capacity to respond to homeostatic cytokines and to specifically lyse MART1-expressing melanoma cells. Furthermore, in a mouse model of melanoma, adoptive transfer of tumor-specific CD8 T cells primed ex vivo in the presence of IFN-α exhibits an improved ability to contain tumor progression. Therefore, exposure to IFN-α during priming of naive CD8 T cells imprints decisive information on the expanded cells that can be exploited to improve the efficacy of adoptive T cell therapy.
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Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T Citotóxicos
/
Citocinas
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Imunização Secundária
/
Interferon-alfa
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Linfócitos T CD8-Positivos
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Homeostase
/
Memória Imunológica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Espanha