Cutting edge: granulocyte-macrophage colony-stimulating factor is the major CD8+ T cell-derived licensing factor for dendritic cell activation.
During priming, CD8(+) T lymphocytes can induce robust maturation of dendritic cells (DCs) in a CD40-independent manner by secreting licensing factor(s). In this study, we isolate this so-far elusive licensing factor and identify it, surprisingly, as GM-CSF. This provides a new face for an old factor with a well-known supporting role in DC development and recruitment. Signaling through the GM-CSFR in ex vivo-purified DCs upregulated the expression of costimulatory molecules more efficiently than did any tested TLR agonist and provided a positive feedback loop in the stimulation of CD8(+) T cell proliferation. Combined with a variety of microbial stimuli, GM-CSF supports the formation of potent "effector" DCs capable of secreting a variety of proinflammatory cytokines that guide the differentiation of T cells during the immune response.
Min
Lin
L
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
Mohammad Isa
Siti Aminah Bte
SA
Shuai
Wang
W
Piang
Cher Boon
CB
Nih
Fam Wee
FW
Kotaka
Masayo
M
Ruedl
Christiane
C
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051820:TCF Transcription Factors / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D018836:Inflammation Mediators; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D051820:TCF Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor