Invariant NKT cells promote CD8+ cytotoxic T cell responses by inducing CD70 expression on dendritic cells.
Activation of invariant NK T (iNKT) cells with the glycolipid alpha-galactosylceramide promotes CD8(+) cytotoxic T cell responses, a property that has been used to enhance the efficacy of antitumor vaccines. Using chimeric mice, we now show that the adjuvant properties of iNKT cells require that CD40 triggering and Ag presentation to CD8(+) T cells occur on the same APCs. We demonstrate that injection of alpha-galactosylceramide triggers CD70 expression on splenic T cell zone dendritic cells and that this is dependent on CD40 signaling. Importantly, we show that blocking the interaction between CD70 and CD27, its costimulatory receptor on T cells, abrogates the ability of iNKT cells to promote a CD8(+) T cell response and abolishes the efficacy of alpha-GalCer as an adjuvant for antitumor vaccines. These results define a key role for CD70 in linking the innate response of iNKT cells to the activation of CD8(+) T cells.
Taraban
Vadim Y
VY
Cancer Sciences Division, University of Southampton, Southampton, UK.
Martin
Sonya
S
Attfield
Kathrine E
KE
Glennie
Martin J
MJ
Elliott
Tim
T
Elewaut
Dirk
D
Van Calenbergh
Serge
S
Linclau
Bruno
B
Al-Shamkhani
Aymen
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D053282:CD27 Ligand / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005699:Galactosylceramides / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D053282:CD27 Ligand; D019013:CD40 Antigens; D005699:Galactosylceramides; D015395:Histocompatibility Antigens Class I