OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice
J. Clin. Invest. Jamal Zaini, et al. 117:3330 doi:10.1172/JCI32693 [
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Figure 1Mice immunized with OVA-pulsed DCs in an OX40L-dependent manner. (
A) Tumor growth in TNF-α–stimulated DCs. Mice were immunized with TNF-α–stimulated DCs pulsed with OVA (filled squares), DCs pulsed with OVA alone (circles), or TNF-α–stimulated DCs alone (triangles), and were challenged with EG7-OVA cells (day 0). Mice without any immunization (open squares) were used as controls. (
B) OVA-specific cytotoxicity in TNF-α–stimulated DCs. Eight days after the immunization described in
A, splenocytes were isolated and assayed for cytolytic function by using EG7-OVA or EL4 cells as target cells. (
C and
D) Flow cytometric analysis of TNF-α–stimulated DCs. DCs from wild-type or OX40L
–/– mice were stimulated with TNF-α and analyzed 2 days later for OX40L (
C) or CD80 expression (
D). Overlay (filled) histograms depict naive DCs. The percentages of stained cells above isotype control staining are shown in each panel. (
E) Role of OX40L on DCs and in tumor growth. TNF-α–stimulated OX40L
–/– (circles) or wild-type DCs (filled squares) pulsed with OVA were used for the immunization challenge experiment. (
F) Role of OX40L on DCs and OVA-specific cytotoxic T cells. Ten days after the immunization described in
E, splenocytes were isolated and analyzed for OVA-reactive CD8
+ T cells (CD8
+H-2K
b/SIINFEKL pentamer
+, boxed) by flow cytometry. The percentage of positive cells is listed. (
G and
H) Flow cytometric analysis of AdOX40L-modified DCs. DCs were transduced with AdOX40L or AdNull and analyzed 2 days later for OX40L (
G) or CD80 expression (
H). The percentages of stained cells above isotype control staining are shown in each panel. (
I) Tumor growth in AdOX40L-modified DCs. AdOX40L- (circles) or AdNull-modified DCs (triangles) pulsed with OVA were used for the immunization challenge experiment. (
J) OVA-specific cytotoxicity of AdOX40L-modified DCs. Eight days after the immunization described in
I, splenocytes were assayed for cytolytic function.