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

ABSTRACT: 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)??. 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?? on CD4(+) helper T cells and LT? 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? production. Therefore, different TNF family members provide integrative signals that shape the licensing potential of antigen-presenting DCs.

SUBMITTER: Summers deLuca L 

PROVIDER: S-EPMC3033245 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

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