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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)