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

Summers deLuca, Leslie, Ng, Dennis, Gao, Yunfei, Wortzman, Michael E., Watts, Tania H., Gommerman, Jennifer L.
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.5 pp. 2046-2051
CD4-positive T-lymphocytes, CD8-positive T-lymphocytes, antigens, dendritic cells, immune response, lymph nodes, lymphotoxin
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.