Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells.
Human thymic stromal lymphopoietin (TSLP) is a novel epithelial cell-derived cytokine, which induces dendritic cell (DC)-mediated CD4+ T cell responses with a proallergic phenotype. Although the participation of CD8+ T cells in allergic inflammation is well documented, their functional properties as well as the pathways leading to their generation remain poorly understood. Here, we show that TSLP-activated CD11c+ DCs potently activate and expand naive CD8+ T cells, and induce their differentiation into interleukin (IL)-5 and IL-13-producing effectors exhibiting poor cytolytic activity. Additional CD40L triggering of TSLP-activated DCs induced CD8+ T cells with potent cytolytic activity, producing large amounts of interferon (IFN)-gamma, while retaining their capacity to produce IL-5 and IL-13. These data further support the role of TSLP as initial trigger of allergic T cell responses and suggest that CD40L-expressing cells may act in combination with TSLP to amplify and sustain pro-allergic responses and cause tissue damage by promoting the generation of IFN-gamma-producing cytotoxic effectors.
Gilliet
Michel
M
DNAX Research Institute, Palo Alto, CA 94304, USA.
Soumelis
Vassili
V
Watanabe
Norihiko
N
Hanabuchi
Shino
S
Antonenko
Svetlana
S
de Waal-Malefyt
Rene
R
Liu
Yong-Jun
YJ
D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008213:Lymphocyte Activation; D000094632:Thymic Stromal Lymphopoietin
D039521:CD11c Antigen; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D023201:CD40 Ligand; D007371:Interferon-gamma; D000094632:Thymic Stromal Lymphopoietin