T cell memory affects lung responses to cecal ligation and puncture.

Murine sepsis models are limited by an inability to recapitulate several common features of human sepsis. One possible explanation is that laboratory mice lack the robust preexisting memory T cell repertoire that is a key feature of the human immune system. We therefore investigated how inducing T cell memory by treating C57BL6 mice with anti-CD3ε activating antibody ("Immune-Educated" mice) affected the pulmonary immune response to the cecal ligation and puncture (CLP)1 model of sepsis. Twenty-four hours after CLP, Immune-Educated mice had higher alveolar inflammatory cytokine and chemokine concentrations and more pulmonary interstitial macrophages than what was observed in untreated ("Uneducated") animals. After 72 hours, there were more alveolar macrophages in the lungs of Educated mice. In a separate experiment, we performed adoptive transfer of memory CD4 and CD8 T cells from immunized C57Bl/6J to B6.SJL mice. Interstitial macrophage recruitment 24 hours post-CLP was more pronounced in mice undergoing adoptive transfer of memory T cells compared to mice that did not undergo adoptive transfer. Finally, to evaluate whether observed differences in CLP-induced lung inflammation between Educated and Uneducated mice are driven by IFN we subjected Educated and Uneducated mice to IFN blockade at the time of CLP. IFN blockade resulted in higher absolute numbers of T cells, memory T cells, and innate cells in the lungs of Educated mice 24 hours post-CLP suggesting that IFN acts as an immune-regulator and curbs an overactive immune response in these mice. In conclusion, the presence of memory T cells affects the course of the lung immune response to CLP.