Brewer, M. R.; Deutschman, C. S.; Taylor, M. D.

Murine sepsis models have not recapitulated human acute respiratory distress syndrome, a major complication of human sepsis. We investigated whether preexisting T cell memory, common in human adults but lacking in laboratory mice, contributes to lung inflammation in the cecal ligation and puncture (CLP) model of sepsis. We compared the pulmonary immune response to CLP in \"Immune-Educated\" mice (treated with anti-CD3{varepsilon} activating antibody to induce T cell memory) to Uneducated controls. Compared to Uneducated mice, 24 hours after CLP, Immune-Educated mice had higher alveolar inflammatory cytokine and chemokine concentrations and more pulmonary interstitial macrophages. After 48 hours, the proportion of effector CD4 T cells that produced interferon-gamma was greater in Immune-Educated mice. After 72 hours, there were more alveolar macrophages in the lungs of Educated mice. Separately, we performed adoptive transfer of memory CD4 and CD8 T cells from immunized C57Bl/6J to B6.SJL mice and IFN{gamma} blockade at the time of CLP. 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. IFN{gamma} 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{gamma} is necessary for curbing an overactive immune response in these mice. In conclusion, the presence of memory T cells affects the course of CLP-induced lung inflammation and may provide a model that more closely resembles sepsis-associated lung injury.