Concomitant activation and antigen uptake via human dectin-1 results in potent antigen-specific CD8+ T cell responses.
J Immunol
; 185(6): 3504-13, 2010 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-20729328
ABSTRACT
Dectin-1, a C-type lectin recognizing fungal and mycobacterial pathogens, can deliver intracellular signals that activate dendritic cells (DCs), resulting in initiation of immune responses and expansion of Th17 CD4(+) T cell responses. In this paper, we studied the roles of human Dectin-1 (hDectin-1) expressed on DCs in the induction and activation of Ag-specific CD8(+) T cell responses. We first generated an agonistic anti-hDectin-1 mAb, which recognizes the hDectin-1 Glu(143)-Ile(162) region. It bound to in vitro monocyte-derived DCs and to in vivo CD1c(+)CD1a(+) dermal DCs but not to epidermal Langerhans cells. Anti-hDectin-1-mediated DC activation resulted in upregulation of costimulatory molecules and secretion of multiple cytokines and chemokines in a Syk-dependent manner. DCs activated with the anti-hDectin-1 mAb could significantly enhance both neo and foreign Ag-specific CD8(+) T cell responses by promoting both the expansion of CD8(+) T cells and their functional activities. We further demonstrated that delivering Ags to DCs via hDectin-1 using anti-hDectin-1-Ag conjugates resulted in potent Ag-specific CD8(+) T cell responses. Thus, hDectin-1 expressed on DCs can contribute to the induction and activation of cellular immunity against intracellular pathogens, such as mycobacteria, that are recognized by DCs via Dectin-1. Vaccines based on delivering Ags to DCs with an agonistic anti-hDectin-1 mAb could elicit CD8(+) T cell-mediated immunity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Proteínas de Membrana
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Proteínas do Tecido Nervoso
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos