LTβR signaling in dendritic cells induces a type I IFN response that is required for optimal clonal expansion of CD8+ T cells

During an immune response, antigen-bearing dendritic cells (DCs) migrate to the local draining lymph node and present antigen to CD4(+) helper T cells. Antigen-activated CD4+ T cells then up-regulate TNF superfamily members including CD40 ligand and lymphotoxin (LT)alpha beta. Although it is well-accepted that CD40 stimulation on DCs is required for DC licensing and cross-priming of CD8(+) T-cell responses, it is likely that other signals are integrated into a comprehensive DC activation program. Here we show that a cognate interaction between LT alpha beta on CD4(+) helper T cells and LT beta receptor on DCs results in unique signals that are necessary for optimal CD8(+) T-cell expansion via a type I IFN-dependent mechanism. In contrast, CD40 signaling appears to be more critical for CD8(+) T-cell IFN gamma production. Therefore, different TNF family members provide integrative signals that shape the licensing potential of antigen-presenting DCs.