Mediastinal lymph node CD8α- DC initiate antigen presentation following intranasal coadministration of α-GalCer

Abstract

Our previous study revealed that α-galactosylceramide (α-GalCer) is a potent nasal vaccine adjuvant inducing both potent humoral and cellular immune responses and affording complete protection against viral infections and tumors. However, the antigen-presenting cells (APC) that are activated by NKT cells and thereby initiate the immune responses following intranasal coadministration of protein antigen and α-GalCer are poorly understood. We assessed here where antigen presentation occurs and which APC subset mediates the early stages of immune responses when protein antigen and α-GalCer are intranasally administered. We show that dendritic cells (DC), but not B cells, initiated the mucosal immune responses at mediastinal lymph nodes. Of the DC subsets, the CD8α -B220-CD11c+ DC subset played the most prominent role in the direct and cross-presentation of protein antigen to naive T cells and in triggering the naive T cells to differentiate into effector T cells. This might be mainly caused by a relatively larger population of CD1dhigh cells of CD8α -B220-CD11c+ DC subset than those of other DC subsets. These results indicate that CD8α -B220-CD11c+ DC is the principal subset becoming immunogenic after interaction with NKT cells and abrogating tolerance to intranasally administered protein antigen when α-GalCer is coadministered as a nasal vaccine adjuvant. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.