Obesity expands a distinct population of adipose-resident T cells and increases vulnerability to infection

Obesity in humans is associated with worsened health outcomes following infections compared to non-obese individuals. Here, we examined the effects of adipose tissue and obesity on T cell responses to virus infection in mice. Lymphocytic choriomeningitis virus (LCMV) grew to high titer in adipose tissue. Virus-specific T cells enter the adipose tissue to resolve infection but then remain as a memory population distinct from memory T cells in lymphoid tissues. Memory CD4+ and CD8+ T cells residing in adipose were abundant, accounting for roughly 10% of all virus-specific memory T cells. Diet-induced obesity increased memory T cell number in adipose and spleen. Upon re-challenge infection, memory T cells caused severe pathogenesis, leading to sharply increased lipase levels, calcification of adipose tissue, pancreatitis, and reduced survival in obese mice but not lean mice. Thus, obesity leads to a unique form of viral pathogenesis involving memory T cell-dependent adipocyte destruction and collateral damage to other tissues. RNA-seq comparison of CD4+ T cells in spleen vs fat (with 10 mice pooled per replicate) and CD8+ T cells in spleen vs fat (with 5 mice pooled per replicate)