Journal Article

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

Svensson-Frej, M, Plantinga, M, Lambrecht, B N, Semmrich, M, Yrlid, U, Agace, W W, Gustafsson, T, Mowat, A M, Uronen-Hansson, H

2012

Overview

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.

• Publisher: Elsevier Inc,Nature Publishing Group US,Elsevier Limited,Nature Publishing Group
• Subject: Allergology / Animals / Antibodies / Antibodies, Monoclonal - genetics / Antibodies, Monoclonal - immunology / Antibodies, Monoclonal - metabolism / Antibody Formation / Antigens / Antigens - genetics / Antigens - immunology / Antigens - metabolism / Antigens, CD - genetics / Antigens, CD - metabolism / Basic Medicine / Biomedical and Life Sciences / Biomedicine / CD4-Positive T-Lymphocytes / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - metabolism / CD4-Positive T-Lymphocytes - pathology / CD8-Positive T-Lymphocytes / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / CD8-Positive T-Lymphocytes - pathology / Cell Proliferation / Cytotoxicity / Cytotoxicity, Immunologic / Dendritic Cells / Dendritic Cells - immunology / Dendritic Cells - metabolism / Dendritic Cells - pathology / Drug Administration Routes / Gastroenterology / genetics / Humans / Immune Tolerance / Immunization / Immunologi inom det medicinska området / Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi) / Immunologic / Immunology / Immunology in the Medical Area / Immunology in the Medical Area (including Cell and Immunotherapy) / Immunomodulation / Integrin alpha Chains / Integrin alpha Chains - genetics / Integrin alpha Chains - metabolism / Knockout / Medical and Health Sciences / Medicin och hälsovetenskap / Medicinska och farmaceutiska grundvetenskaper / metabolism / Mice / Mice, Knockout / Monoclonal / Ovalbumin / Ovalbumin - genetics / Ovalbumin - immunology / Ovalbumin - metabolism / pathology / Protein Engineering / Recombinant Fusion Proteins / Recombinant Fusion Proteins - genetics