%A Taylor,Matthew D. %A Fernandes,Tiago D. %A Kelly,Alexander P. %A Abraham,Mabel N. %A Deutschman,Clifford S. %D 2020 %J Frontiers in Immunology %C %F %G English %K cecal ligation and puncture,Sepsis,innate immunity,Organ dysfunction,T cell memory,CD4 T cells,CD8 T cells,Adaptive Immunity %Q %R 10.3389/fimmu.2020.563402 %W %L %M %P %7 %8 2020-November-20 %9 Original Research %+ Matthew D. Taylor,The Division of Critical Care Medicine, Department of Pediatrics, The Feinstein Institutes for Medical Research, Manhasset, NY, and Cohen Children’s Medical Center/Northwell Health,United States,mtaylor15@northwell.edu %+ Matthew D. Taylor,Sepsis Research Laboratory, The Feinstein Institutes for Medical Research,United States,mtaylor15@northwell.edu %# %! T cell memory alters responses to CLP %* %< %T CD4 and CD8 T Cell Memory Interactions Alter Innate Immunity and Organ Injury in the CLP Sepsis Model %U https://www.frontiersin.org/articles/10.3389/fimmu.2020.563402 %V 11 %0 JOURNAL ARTICLE %@ 1664-3224 %X The role of T cell memory in sepsis is poorly understood. Recent work has demonstrated that mice exposed to frequent antigenic stimulation, in contrast to laboratory mice, better recapitulate the human T cell repertoire. This difference may profoundly alter responses to inflammatory insults. We induced isolated T cell memory by inoculating C57Bl/6 mice with an anti-CD3ϵ activating antibody, a process we term “immune education.” These mice were subjected to the cecal ligation and puncture (CLP) model of sepsis and responses were compared to those of isotype-treated controls. CLP-induced increases in 1) CD4 T cell production and serum levels of IFNγ, 2) CD8 T cell granzyme B levels, and 3) innate cell function were all more pronounced in educated mice than in control mice. Immune education increased CLP-induced liver injury and decreased survival. The differences in responses to CLP were not recapitulated in mice with either isolated CD4 or isolated CD8 T cell memory. Relative to controls, CLP in educated CD8−/− mice (isolated CD4 memory) increased monocyte-derived dendritic cells. Combined CD4 and CD8 memory did not increase monocyte-derived dendritic cells; this combination recapitulated increases in neutrophil and inflammatory monocyte numbers in educated wild-type mice. Induction of T cell memory prior to CLP alters immune responses, organ function, and survival. Both CD4 and CD8 memory T cells play important and independent roles in this response. These findings have profound implications for the development of murine models of human inflammatory disorders such as infection and sepsis.