Protective anti-mycobacterial T cell responses through exquisitein vivo activation of vaccine-targeted dendritic cells

Autor: Anne-Françoise Rochat, Claire-Anne Siegrist, Karen Lingnau, Else Marie Agger, Arun T. Kamath, Paul-Henri Lambert, Mario Paolo Valenti, Alexander von Gabain, Peter Andersen
Rok vydání: 2008
Předmět:
CD4-Positive T-Lymphocytes
Alum Compounds/administration & dosage
Antigens
CD11c/analysis
Mycobacterium bovis/immunology
Oligodeoxyribonucleotides/pharmacology
T-Lymphocytes
medicine.medical_treatment
ddc:616.07
Lymphocyte Activation
Mice
Recombinant Fusion Proteins/administration & dosage/analysis/immunology
Immunology and Allergy
Bacterial Proteins/genetics/immunology
Antigen Presentation
education.field_of_study
ddc:618
biology
Tuberculosis/immunology/prevention & control
Interleukin-12 Subunit p40
Vaccination
Mycobacterium bovis
Ovalbumin/administration & dosage/immunology
medicine.anatomical_structure
Oligodeoxyribonucleotides
CD4-Positive T-Lymphocytes/immunology
Alum Compounds
Spleen/cytology/immunology/microbiology
Antigens
Bacterial/genetics/immunology
Adjuvant
Ovalbumin
Recombinant Fusion Proteins
T cell
Immunology
Population
Lymphocyte Activation/immunology
Interleukin-12 Subunit p40/metabolism
Interferon-gamma
Adjuvants
Immunologic
Bacterial Proteins
Antigens
CD
In vivo
medicine
Lymph Nodes/cytology/immunology
Animals
Tuberculosis
T-Lymphocytes/immunology/metabolism
Vaccination/methods
Antigen Presentation/immunology
education
Interferon-gamma/metabolism
Cell Proliferation
CD86
Antigens
Bacterial
CD40
Antigens
CD/analysis/metabolism
Dendritic Cells/drug effects/immunology/metabolism
Dendritic Cells
Vaccine efficacy
CD11c Antigen
Mice
Inbred C57BL
Adjuvants
Immunologic/administration & dosage/analysis
biology.protein
Lymph Nodes
Spleen
CD80
Zdroj: European Journal of Immunology, Vol. 38, No 5 (2008) pp. 1247-56
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.200737889
Popis: Vaccine efficacy largely depends upon DC targeting and activation. The most potent TLR soluble ligands induce diffuse DC activation, which may be associated with marked pro-inflammatory responses and possibly adverse effects. This raises the concern that effective vaccine adjuvants may similarly rely on widespread DC activation. Using a promising candidate vaccine against tuberculosis (fusion protein of Ag85B and 6-kDa early secretory antigenic target (ESAT-6)) formulated in the potent IC31 adjuvant, DC targeting and activation was studied in vivo, following the fate of antigen and adjuvant in the draining lymph nodes, to define the magnitude of DC targeting/activation required in vivo to induce protective vaccine responses. Unexpectedly, protective IFN-gamma-mediated Ag85B-ESAT-6/IC31 responses were associated to the activation of a minute population (less than 0.3%) of CD11c(+) lymph node DC, without detectable systemic pro-inflammatory responses. This activated peripheral tissue-derived DC population, characterized by enhanced CD80, CD86, CD40 and IL-12p40 expression, was only identified when focusing on adjuvant- or antigen-labeled CD11c(+) DC, which were found to support T cell proliferation. Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen-associated DC but without detectable enhancement of CD80, CD86, CD40 or IL-12p40 expression. Thus, potent protective IFN-gamma-producing responses may be elicited by the exquisite activation of a minute number of in vivo targeted DC.
Databáze: OpenAIRE
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