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

Mucosal Immunol. 2012 Mar;5(2):150-60. doi: 10.1038/mi.2011.61. Epub 2011 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antibody Formation
  • Antigens / genetics
  • Antigens / immunology
  • Antigens / metabolism
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Proliferation
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Drug Administration Routes
  • Humans
  • Immune Tolerance
  • Immunization
  • Immunomodulation
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism*
  • Mice
  • Mice, Knockout
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Protein Engineering
  • Recombinant Fusion Proteins / genetics

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Antigens, CD
  • Integrin alpha Chains
  • Recombinant Fusion Proteins
  • alpha E integrins
  • Ovalbumin