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 [Go to this article.]

Figure 5
Depletion of cytokine sinks, removal of Tregs, and activation of the innate immune system recapitulate the effectiveness of TBI. (A) Activation of the innate immune system with serum LPS, depletion of Tregs with anti-CD4 antibody, and removal of cytokine sinks with anti-NK antibody are required to improve the efficacy of adoptively transferred in nonirradiated mice. Tumor-bearing C57BL/6 mice received 5 Gy TBI or were left nonirradiated. Alternatively, mice were depleted of lymphocytes with CD4 and NK antibodies; 1 day later mice received 5 × 10⁵ cultured pmel-1 T cells, rFPhgp100 vaccination, and IL-2. Serum for irradiated mice containing LPS was harvested and transferred into nonirradiated recipients. (B) Ultrapure LPS enhanced treatment in lymphodepleted nonirradiated mice. C57BL/6 mice were irradiated as a control. Mice received serum with translocated LPS or ultrapure LPS alone, CD4 alone, or NK-depleting antibody alone 1 day after ACT. Data (mean ± SEM; n = 4–5 per group) are representative of 2 independent experiments. (C) Ultrapure LPS recapitulated the effectiveness of TBI in Rag2^–/–γ_c^–/– mice genetically deficient in all lymphocytes. Data (mean ± SEM; n = 5 per group) are representative of 2 independent experiments. ^†P = 0.05 versus irradiated treated mice. The difference between the nonirradiated, treated, LPS-administered group and the irradiated treated group was not significant (P < 0.2).