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)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.
Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8.
Leslie
L
Summers deLuca
Dennis
D
Ng
Yunfei
Y
Gao
Michael E
ME
Wortzman
Tania H
TH
Watts
Jennifer L
JL
Gommerman
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002455:Cell Division; D002460:Cell Line; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D053259:Lymphotoxin beta Receptor / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
D007370:Interferon Type I; D053259:Lymphotoxin beta Receptor
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