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 3Ciprofloxacin treatment impairs the effectiveness of ACT therapy and reduces activation of the innate immune system in irradiated mice. (
A) Ciprofloxacin reduced the detectable level of LPS in serum. Serum from nonirradiated and 5 Gy irradiated mice left untreated or treated with ciprofloxacin (Cipro) was collected and analyzed for the presence of microbial LPS using a limulus amebocyte lysate assay. Data (
n = 3 per group) are representative of 2 independent experiments. (
B) Ciprofloxacin treatment reduced the absolute number of host DCs. One day after TBI, splenocytes were isolated from nonirradiated and 5 Gy irradiated mice left untreated or treated with ciprofloxacin. Absolute numbers of CD11c
+CD86
high DCs were determined in the spleens of nonirradiated and irradiated mice. Data (
n = 3 per group) are representative of 2 independent experiments. Horizontal bars indicate means. (
C) Treatment of irradiated hosts with ciprofloxacin reduced effectiveness of ACT treatment. C57BL/6 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. Administration of ciprofloxacin as indicated began 2 days prior to ACT and continued for 2 weeks after treatment. Data (mean ± SEM;
n = 4–5 per group) are representative of 2 independent experiments.
†P = 0.05,
††P < 0.05 versus 5 Gy TBI without ciprofloxacin;
‡‡P < 0.001 versus 5 Gy TBI plus treatment without ciprofloxacin.