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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-02, Vol.108 (5), p.2046-2051
• Main Authors: Summers deLuca, Leslie, Ng, Dennis, Gao, Yunfei, Wortzman, Michael E, Watts, Tania H, Gommerman, Jennifer L
• Format: Article
• Language: English
• Subjects: Agonists; Animals; Antigen presentation; Biological Sciences; CD4 antigen; CD40 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; Cell activation; Cell Division; Cell Line; Cell migration; Coculture techniques; Cross priming; Dendritic cells; Humans; Immunity; Interferon; Interferon Type I - biosynthesis; Ligands; Ligation; Lymph nodes; Lymphocyte Activation; Lymphocytes T; Lymphotoxin; Lymphotoxin beta Receptor - metabolism; Mice; Mice, Inbred C57BL; Ova; Receptors; Signal Transduction; T lymphocytes; Tumor necrosis factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1014188108

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)αβ. 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 LTαβ on CD4⁺ helper T cells and LTβ 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 IFNγ production. Therefore, different TNF family members provide integrative signals that shape the licensing potential of antigen-presenting DCs.