The lung vascular filter as a site of immune induction for T cell responses to large embolic antigen
| Autor: | Kim Deswarte, Henk C. Hoogsteden, Monique Willart, Louis Boon, Bart N. Lambrecht, Björn E. Clausen, Thomas Soullié, Hamida Hammad, Hendrik Jan de Heer |
|---|---|
| Přispěvatelé: | Amsterdam institute for Infection and Immunity, Cell Biology and Histology, Pulmonary Medicine, Surgery, Immunology |
| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer T cell Immunology Biology CD8-Positive T-Lymphocytes Monocytes Article Mice Immune system Antigen medicine Immunology and Allergy Cytotoxic T cell Animals Antigens CD40 Antigens Lung Mice Inbred BALB C CD40 Mediastinum Dendritic Cells Acquired immune system Immunity Humoral Toll-Like Receptor 4 medicine.anatomical_structure biology.protein Female Lymph Nodes CD8 Cell Division |
| Zdroj: | The Journal of Experimental Medicine Journal of experimental medicine, 206(12), 2823-2835. Rockefeller University Press Journal of Experimental Medicine, 206(12), 2823-2835. Rockefeller University Press |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | The bloodstream is an important route of dissemination of invading pathogens. Most of the small bloodborne pathogens, like bacteria or viruses, are filtered by the spleen or liver sinusoids and presented to the immune system by dendritic cells (DCs) that probe these filters for the presence of foreign antigen (Ag). However, larger pathogens, like helminths or infectious emboli, that exceed 20 µm are mostly trapped in the vasculature of the lung. To determine if Ag trapped here can be presented to cells of the immune system, we used a model of venous embolism of large particulate Ag (in the form of ovalbumin [OVA]-coated Sepharose beads) in the lung vascular bed. We found that large Ags were presented and cross-presented to CD4 and CD8 T cells in the mediastinal lymph nodes (LNs) but not in the spleen or liver-draining LNs. Dividing T cells returned to the lungs, and a short-lived infiltrate consisting of T cells and DCs formed around trapped Ag. This infiltrate was increased when the Toll-like receptor 4 was stimulated and full DC maturation was induced by CD40 triggering. Under these conditions, OVA-specific cytotoxic T lymphocyte responses, as well as humoral immunity, were induced. The T cell response to embolic Ag was severely reduced in mice depleted of CD11chi cells or Ly6C/G+ cells but restored upon adoptive transfer of Ly6Chi monocytes. We conclude that the lung vascular filter represents a largely unexplored site of immune induction that traps large bloodborne Ags for presentation by monocyte-derived DCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|