TY - JOUR
T1 - Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses
AU - Ni, Ling
AU - Gayet, Ingrid
AU - Zurawski, Sandra
AU - Duluc, Dorothee
AU - Flamar, Anne Laure
AU - Li, Xiao Hua
AU - O'Bar, Amy
AU - Clayton, Sandra
AU - Palucka, Anna Karolina
AU - Zurawski, Gerard
AU - Banchereau, Jacques
AU - Oh, Sang Kon
PY - 2010/9/15
Y1 - 2010/9/15
N2 - 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 Glu143-Ile162 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. Copyright
AB - 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 Glu143-Ile162 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. Copyright
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U2 - 10.4049/jimmunol.1000999
DO - 10.4049/jimmunol.1000999
M3 - Article
C2 - 20729328
AN - SCOPUS:78649902080
SN - 0022-1767
VL - 185
SP - 3504
EP - 3513
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -