Expression of lymphotoxin-αβ on antigen-specific T cells is required for DC function

During an immune response, activated antigen (Ag)-specific T cells condition dendritic cells (DCs) to enhance DC function and survival within the inflamed draining lymph node (LN). It has been difficult to ascertain the role of the tumor necrosis factor (TNF) superfamily member lymphotoxin-alpha beta (LT alpha beta) in this process because signaling through the LT beta-receptor (LT beta R) controls multiple aspects of lymphoid tissue organization. To resolve this, we have used an in vivo system where the expression of TNF family ligands is manipulated only on the Ag-specific T cells that interact with and condition Ag-bearing DCs. We report that LT alpha beta is a critical participant required for optimal DC function, independent of its described role in maintaining lymphoid tissue organization. In the absence of LT alpha beta or CD40L on Ag-specific T cells, DC dysfunction could be rescued in vivo via CD40 or LT beta R stimulation, respectively, suggesting that these two pathways cooperate for optimal DC conditioning.