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Directed antigen targeting in vivo identifies a role for CD103(+) dendritic cells in both tolerogenic and immunogenic T-cell responses.

Journal article
Authors M Semmrich
M Plantinga
M Svensson-Frej
H Uronen-Hansson
Tobias Gustafsson
A M Mowat
Ulf Yrlid
B N Lambrecht
W W Agace
Published in Mucosal immunology
Volume 5
Issue 2
Pages 150-60
ISSN 1935-3456
Publication year 2012
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 150-60
Language en
Links dx.doi.org/10.1038/mi.2011.61
Keywords Animals, Antibodies, Monoclonal, genetics, immunology, metabolism, Antibody Formation, Antigens, genetics, immunology, metabolism, Antigens, CD, genetics, metabolism, CD4-Positive T-Lymphocytes, immunology, metabolism, pathology, CD8-Positive T-Lymphocytes, immunology, metabolism, pathology, Cell Proliferation, Cytotoxicity, Immunologic, Dendritic Cells, immunology, metabolism, pathology, Drug Administration Routes, Humans, Immune Tolerance, Immunization, Immunomodulation, Integrin alpha Chains, genetics, metabolism, Mice, Mice, Knockout, Ovalbumin, genetics, immunology, metabolism, Protein Engineering, Recombinant Fusion Proteins, genetics
Subject categories Immunobiology

Abstract

The αE integrin chain CD103 identifies a subset of migratory dendritic cells (DCs) in the gut, lung, and skin. To gain further understanding of the function of CD103(+) DCs in regulating adaptive immunity in vivo, we coupled ovalbumin (OVA) to the CD103 antibody M290 (M290.OVA). Intraperitoneal injection of M290.OVA induced OVA-specific CD8(+) and CD4(+) T-cell proliferation in lymph nodes (LNs) of wild-type but not CD103(-/-) mice, or in mice depleted of CD11c(+) cells. In the absence of maturation stimuli, systemic antigen targeting to CD103(+) DCs led to tolerance of CD8(+) T cells, whereas coadministration of adjuvant induced cytotoxic T-lymphocyte (CTL) immunity and antibody production. Mucosal intratracheal application of M290.OVA also induced T-cell proliferation in mediastinal LNs, yet the functional outcome was tolerance that inhibited subsequent development of allergic airway inflammation and immunoglobulin E (IgE) responses to inhaled OVA. These findings identify antigen targeting to CD103(+) DCs as a potential strategy to regulate immune responses in nonlymphoid mucosal tissues.

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