Sleeve Gastrectomy Restores Mucosal CD8+ t-cell Immunity.
David A. Harris, MD, Renuka Subramaniam, PHD, Keyvan Heshmati, MD, Ali Tavakkoli, Eric Sheu MD, PhD
Brigham and Women's Hospital, Boston, MA, USA
Background: Changes in the gut milieu partially underlie the benefits of sleeve gastrectomy (SG). The host mucosal immune populations represent a possible mechanism through which benefits are realized. Thus, we hypothesized that jejunal mucosal lymphocyte populations contribute to diabetes resolution and weight loss in a mouse model of SG.
Methods: C57Bl/6J mice were placed into four groups – normal chow (n=6); high fat diet (HFD) without intervention (n=6); HFD with SG (n=6); HFD with sham (n=7). Jejunal specimen were harvested for time of flight mass cytometry (CyTOF) analysis and visualization of stochastic neighbor embedding (ViSNE) was used for unbiased population identification. A 24 antibody CyTOF panel enabled in-depth cellular profiling across adaptive and innate lymphocyte populations.
Results: ViSNE (figure 1a; heat map signifies staining frequency) of jejunal populations revealed a 28% increase in the percentage of CD8+ lymphocytes that were CD103+ following SG as compared to shams (65.6±14 and 37.1±19; p=0.01). Interestingly, when comparing CD8+ populations in non-operated NCD and HFD mice, there was a 49% reduction in the CD8+103+ population with HFD (85.2±7 and 36.8±10; p=0.002; figure 1b). These findings were validated by flow cytometry and mirrored improvements in glucose homeostasis and weight.
Conclusion: There is a dramatic normalization of the mucosal immune state following SG. This is realized as a transition of CD8+103- to CD8+103+ cells. This transition may underlie the benefits of SG.
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