Ectopic lung transplantation induces the accumulation of eosinophil progenitors in the recipients' lungs through an allergen- and interleukin-5-dependent mechanism.

BACKGROUND: Airway challenge of ovalbumin-sensitized mice induces intrapulmonary accumulation of eosinophil progenitors.
OBJECTIVE: To evaluate whether allergen-challenged lungs release factors promoting intrapulmonary accumulation of haemopoietic cells, and define the role of allergic lung injury, we developed a transplantation model.
METHODS: Lung tissue from allergen-challenged, sensitized donors was ectopically grafted in syngeneic recipients, and haemopoietic progenitors inside the lungs of the recipients were quantified.
RESULTS: In BALB/c mice, accumulation of progenitors occurred only when: (a) donors were sensitized and airway challenged with homologous allergen; (b) and recipients were sensitized. Grafts from the appropriate donors released biologically active IL-5, which was effective in sensitized recipients. The effect of the appropriate donor-recipient combination was prevented by neutralizing anti-IL-5 antibody. Grafts from unchallenged, sensitized donors synergized with recombinant IL-5 in sensitized recipients. Unlike BALB/c, grafts from naïve IL-5 transgenic CBA/Ca mice (whose lungs contained a large number of progenitors, independently of sensitization and challenge) were effective in non-transgenic, ovalbumin-sensitized recipients.
CONCLUSION: This shows that: (a) intrapulmonary accumulation of progenitors is independent of immunological injury; (b) grafts systemically release IL-5, which is required for progenitor accumulation in the recipients' lungs; (c) and sensitization is required for full responsiveness to IL-5 and for generation of lung-derived signals that synergize with IL-5.