Mediastinal lymph node CD8alpha- DC initiate antigen presentation following intranasal coadministration of alpha-GalCer.
Our previous study revealed that alpha-galactosylceramide (alpha-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 alpha-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 alpha-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 CD8alpha-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 CD8alpha-B220-CD11c+ DC subset than those of other DC subsets. These results indicate that CD8alpha-B220-CD11c+ DC is the principal subset becoming immunogenic after interaction with NKT cells and abrogating tolerance to intranasally administered protein antigen when alpha-GalCer is coadministered as a nasal vaccine adjuvant.
Ko
Sung-Youl
SY
Laboratory of Immunology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Lee
Kyoo-A
KA
Youn
Hyun-Jun
HJ
Kim
Yeon-Jeong
YJ
Ko
Hyun-Jeong
HJ
Heo
Tae-Hwe
TH
Kweon
Mi-Na
MN
Kang
Chang-Yuil
CY
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology; D055610:Antigens, CD1d; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000008:administration & dosage* / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008482:Mediastinum / Q000502:physiology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin