T cell memory alters pulmonary inflammatory responses to cecal ligation and puncture.

To date, murine sepsis models have failed to recapitulate human acute respiratory distress syndrome, one of the leading complications of human sepsis. We set out to determine if preexisting T cell memory, which is common in human adults and lacking in laboratory mice, could contribute to lung inflammation in the cecal ligation and puncture (CLP) model of sepsis. After administering an anti-CD3ε activating antibody to C57Bl/6 mice to induce a T cell memory repertoire, we compared the pulmonary immune response to CLP in these "Immune-Educated mice" to responses observed in Uneducated control animals. 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 IFNγ 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. IFNγ 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 IFNγ 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.