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Responses to LPS boost effector CD8 T-cell accumulation outside of signals 1 and 2

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Abstract

Immunization with adjuvant plus antigen induces durable T-cell immunity and is a mainstay of vaccines. Here, the consequence of separating antigen stimulation of T cells from the adjuvant response was studied in a re-transfer model. Effector CD8 T cells in recipient mice were exposed to lipopolysaccharide (LPS), the Toll-like receptor 4 (TLR4) ligand, which significantly increased persistence. While accumulation in lymphoid and non-lymphoid organs was evident, this result depended upon the timing of LPS administration and the presence of the TLR4 adaptor TRIF in the recipient mice. Interestingly, there was very little impact of the LPS response on subset differentiation, which rather appeared to be programmed by antigen and costimulation. To discern factors that limit accumulation, interleukin 10 (IL-10) was targeted since it is a product of TLR4 triggering and mitigates inflammation. Blockade of IL-10 increased accumulation even though the effector CD8 T cells were well past the priming phase, but upon recall interferon-γ secretion was not affected as would be expected when IL-10 is present during priming. Thus, the adjuvant-altered microenvironment is effective not only in the presence of antigen but also during a window of effector CD8 T-cell stasis, suggesting that pathogen-associated molecular pattern molecules released during co-infection, or by vaccines, could alter the survival fate of specific effector T cells.

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Acknowledgements

The authors would like to thank Drs. Adam Adler and Robert Clark for helpful discussions. Funding was provided by NIH/NIAID 2RO1 AI0142858-12A1 (Anthony T. Vella), and the research was developed by (Anthony T. Vella), while the studies were completed by (Wenhai Liu), and (Antoine Menoret) contributed key preliminary data on model development and assistance. The manuscript jointly written by (Anthony T. Vella) and (Wenhai Liu), and edited by (Antoine Menoret).

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  1. Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, 06030, CT, USA

    Wenhai Liu, Antoine Menoret & Anthony T Vella

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Correspondence to Anthony T Vella.

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Liu, W., Menoret, A. & Vella, A. Responses to LPS boost effector CD8 T-cell accumulation outside of signals 1 and 2. Cell Mol Immunol 14, 254–264 (2017). https://doi.org/10.1038/cmi.2015.69

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