Dendritic cells (DCs) are considered to be the most efficient antigen-presenting cells. Intratracheal administration of
allergen-pulsed bone marrow-derived dendritic cells (BMDCs) before
allergen challenge induces
airway hyperresponsiveness (AHR) and
inflammation.
Ovalbumin (OVA)-pulsed BMDCs from wild-type (WT) mice were transferred into naive WT, CD4(-/-), CD8(-/-), or
IL-13(-/-) mice. Two days (short protocol) or 10 days (long protocol) after BMDC transfer, mice were challenged with 1% OVA for 3 days and assayed 2 days later. Transfer of OVA-primed BMDCs into BALB/c or C57BL/6 mice elicited AHR in both protocols. Airway
eosinophilia, Th2
cytokines, or goblet cell
metaplasia were increased in the long but not short protocol. Lung T cells from both protocols produced Th2
cytokines in response to OVA in vitro.
Carboxyfluorescein diacetate succinimidylester-labeled BMDCs were observed in bronchoalveolar lavage (BAL) fluid and lung parenchyma at early time points, and were detected in draining lymph nodes 48 hours after transfer. CD8(-/-) mice developed AHR comparable to WT mice in the short protocol, but decreased levels of AHR, airway
eosinophilia, Th2
cytokines in BAL fluid, and goblet cell
metaplasia compared with WT mice in the long protocol. CD4(-/-) or
IL-13(-/-) mice did not develop AHR or airway
inflammation in either protocol. These data suggest that
allergen-pulsed BMDCs initiate development of AHR that is dependent initially on CD4(+) T cells, and at later time periods on CD8+ T cells and
IL-13. Thus, the timing of
allergen challenge after transfer of
allergen-pulsed BMDC affects the development of AHR and airway
inflammation.