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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

Author:
Summers deLuca, Leslie, Ng, Dennis, Gao, Yunfei, Wortzman, Michael E., Watts, Tania H., Gommerman, Jennifer L.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.5 pp. 2046-2051
ISSN:
0027-8424
Subject:
CD4-positive T-lymphocytes, CD8-positive T-lymphocytes, antigens, dendritic cells, immune response, lymph nodes, lymphotoxin
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)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.
Agid:
2371623