Allergen-induced changes in bone-marrow progenitor and airway dendritic cells in sensitized rats

Eosinophilic airway inflammation is orchestrated by T-helper (Th)-2 lymphoc ytes. We have previously demonstrated that dendritic cells (DC) an essentia l for the presentation of antigen to these Th2 cells leading to airway infl ammation. Here, we have examined the presence of DC in the lungs, the kinet ics of appearance, and the possible involvement of the bone-marrow progenit or for DC in a rat model of ovalbumin (OVA)-induced airway inflammation. Se nsitized rats were exposed to 0, 1, 3, or 7 consecutive daily OVA aerosols. Control rats were sham sensitized and/or exposed to phosphate-buffered sal ine (PBS), and bronchoalveolar lavage (BAL) was performed 24 h after the la st challenge. DC were identified in BAL fluid as low-density, low-autofluor escence, CD3(-), CD45RA(-), OX62(+), OX6(+) cells that had long surface ext ensions and strong costimulatory activity. Low but detectable amounts of BA L DC were seen in sensitized, unexposed animals. After three OVA exposures, the inflammatory infiltrate consisted of CD4(+)-activated T cells, eosinop hils, and monocytes. The number of BAL DC was significantly increased in OV A-sensitized/OVA-exposed animals compared with sham-sensitized or PBS-expos ed animals. The kinetics of DC inc ease closely parallelled those in other inflammatory cells. Bone-marrow cells taken from the OVA-sensitized and -ex posed group were grown in the DC growth factor granulocyte macrophage colon y-stimulating factor for 6 d and the yield of OX62(+)OX6(+) DC was 60% high er compared with PBS-exposed or sham-sensitized animals. We conclude that a llergen exposition in sensitized rats increases the number of DC in the air ways and the production of progenitors for DC in the bone marrow.