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Proc Natl Acad Sci U S A ; 110(41): 16550-5, 2013 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-24052528

RESUMO

Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Citomegalovirus/imunologia , Vetores Genéticos/imunologia , Evasão da Resposta Imune/imunologia , Proteínas de Membrana/metabolismo , Vacinas Sintéticas/imunologia , Animais , Citomegalovirus/genética , Citometria de Fluxo , Vetores Genéticos/genética , Listeria monocytogenes/imunologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Estatísticas não Paramétricas
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