Peribronchiolar accumulation of dendritic cells and their close association with CD4⁺ T cells in the murine lung hypersensitivity

Abstract

In order to understand the interaction between dendritic cells (DCs) and helper T (Th) cells in the region exposed to antigens during pulmonary delayed-type hypersensitivity (DTH), which is considered to be mediated by Th1 cells, we immunohistochemically investigated their spatial relationship in the cellular infiltrate. At 24 hours after intratracheal instillation of hapten in sensitized mice, DCs were preferentially accumulated around the bronchioles, whereas macrophages were more abundant around the accompanying arteries. DCs often formed a cluster, in which they were interconnected with each other by projections. Serial section analysis revealed that clustered DCs made a close apposition to Th cells but much less frequently to cytotoxic T cells and B cells. Immunoelectron microscopy demonstrated that lymphocytes extravasated the capillaries in the peribronchiolar interstitium and made conjugation with DCs. In the interstitial tissue, DCs often adhered to the fibroblasts, suggesting the supportive role of the latter cells in DC migration. Eosinophils were also frequent around the arteries, representing the possible involvement of Th2 cytokines. By contrast, in a chronic type of airway inflammation induced by repeated challenges of aerosolized ovalbumin, DCs were densely and diffusely accumulated around the arteries in the same way as macrophages. The present study demonstrated a close association of DCs with Th cells around the bronchioles during pulmonary DTH, suggesting that local interaction between them in the lung may play important roles in the development of this disorder.

Leukocyte Infiltration of the Periarterial Space of the Lung after Allergen Provocation in a Rat Asthma Model

“…Our electron-microscopic fi ndings are in accordance with the results of other authors [25,26] . In a chronic ovalbumin model, Nishida et al [25] showed that eosinophils were frequent around the arteries and that lymphocytes left capillaries in the peribronchiolar interstitial space.…”

“…In a chronic ovalbumin model, Nishida et al [25] showed that eosinophils were frequent around the arteries and that lymphocytes left capillaries in the peribronchiolar interstitial space. Studies by Ichikawa et al [26] discovered periarterial accumulation of leukocytes in the lung after intratracheal administration of sheep erythrocyte antigen to primed mice.…”

Lymphocyte Activation in the Lungs of SP-D Null Mice

“…Such collections are not uniform and are often observed in association with enlarged macrophages, suggesting that SP-D Ϫ/Ϫ macrophages might be responsible for accumulation of lymphocytes. Similar collections of lymphocytes have been described in several models of lung inflammation that are mediated by specific immunoreactivity to inhaled antigens (14)(15)(16). Our colony of SP-D Ϫ/Ϫ mice is maintained under standard vivarium conditions.…”

The Periarterial Space in the Lung: Its Important Role in Lung Edema, Transplantation, and Microbial or Allergic Inflammation

“…The role of dendritic cells (DC) in the OVA model has been repeatedly shown. Nishida et al [34] documented by microscopical and ultrastructural techniques that DC, eosinophils and lymphocytes were next to vessels in a chronic OVA model at 24 h and lymphocytes emigrated via capillaries. When OVA-pulsed DC were instilled into the trachea of rats and these animals challenged for 3 days, a dramatic accumulation of mononuclear cells in the periarterial space was seen [35,36].…”