This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0256OCv1 41/3/271    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Koya, T. Articles by Gelfand, E. W. PubMed PubMed Citation Articles by Koya, T. Articles by Gelfand, E. W.

Differential Effects of Dendritic Cell Transfer on Airway Hyperresponsiveness and Inflammation

¹ Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado

Correspondence and requests for reprints should be addressed to Erwin W. Gelfand, M.D., Department of Pediatrics, Division of Cell Biology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206. E-mail: gelfande{at}njc.org

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.

Key Words: dendritic cells • CD8⁺ T cells • airway hyperresponsiveness