Induction of rapid T cell activation, division, and recirculation by intratracheal injection of dendritic cells in a TCR transgenic model

Dendritic cells (DCs) are thought to be responsible for sensitization to in haled Ag and induction of adaptive immunity in the lung. The characteristic s of T cell activation in the lung were studied after transfer of Ag-pulsed bone marrow-derived DCs into the airways of naive mice. Cell division of A g-specific T cells in vivo was followed in a carboxyfluorescein diacetate s uccinimidyl ester-labeled cohort of naive moth cytochrome c-reactive TOR tr ansgenic T cells, Our adoptive transfer system was such that transferred DC s were the only cells expressing the MHC molecule required for presentation of cytochrome c to transgenic T cells. Ag-specific T cell activation and p roliferation occurred rapidly ire the draining lymph nodes of the lung, but not in nondraining lymph nodes or spleen. No bystander activation of non-A g-specific T cells was induced. Division of Ag-specific T cells was accompa nied by transient expression of CD69, while up-regulation of CD44 increased with each cell division. Divided cells had recirculated to nondraining lym ph nodes and spleen by day 4 of the response. In vitro restimulation with s pecific Ag revealed that T cells were primed to proliferate more strongly a nd to produce higher amounts of cytokines per cell. These data are consiste nt with the notion that DCs in the lung are extremely efficient in selectin g Ag-reactive T cells from a diverse repertoire. The response is initially localized in the mediastinal lymph nodes, but subsequently spreads systemic ally, This system should allow us to study the early events leading to sens itization to inhaled Ag.