Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling
J. Clin. Invest. Chrystal M. Paulos, et al. 117:2197 doi:10.1172/JCI32205 [
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Figure 6Administration of ultrapure LPS after TBI significantly enhances antitumor immunity and autoimmunity. (
A) Ultrapure LPS augmented antitumor responses in irradiated mice. Mice bearing s.c. B16F10 tumors established for 10 days received 5 Gy TBI. One day later, mice received an ACT treatment consisting of adoptive transfer of 10
6 cultured pmel-1 T cells, rFPhgp100 vaccination, and rhIL-2 or were left untreated. The next day, mice received ultrapure LPS or were left untreated. Data (mean ± SEM;
n = 5–10 per group) are representative of 10 independent experiments. (
B) LPS enhanced autoimmune vitiligo in irradiated mice. One month after ACT treatment, irradiated mice treated with or without ultra-pure LPS were evaluated for the development of vitiligo. Mice were scored for the degree of hypopigmentation on a scale of 0–5. Data (
n = 4–5 per group) are from 3 independent experiments. Horizontal bars indicate means. (
C) Ultrapure LPS increased the absolute number of transferred pmel-1 T cells in the irradiated host. Absolute numbers of transferred pmel-1 T cells (CD8
+Thy1.1
+) in irradiated host. Data (mean ± SEM;
n = 3–5 per group) are representative of 2 independent experiments. (
D) Ultrapure LPS enhanced the function of adoptively transferred cells in irradiated mice. Five days after ACT treatment, pmel-1–Thy1.1
+ splenocytes were cocultured with irradiated splenocytes pulsed with the indicated doses of hpg100
25–33. Unpulsed splenocytes were used as controls. Data (mean ± SEM;
n = 3 per group) are representative of 2 independent experiments.
††P < 0.05,
‡‡P < 0.001 versus irradiated treated mice.