Diet induced obesity has an influence on intrahepatic T cell responses

Obesity is accompanied with systemic inflammation and pre-conditions to severe alterations in liver environment and functions. So far, it remains elusive to which extent obesity modulates immune responses during hepatotropic virus infections as well as in autoimmune hepatitis. In this study we investigated the influence of obesity on the intrahepatic immune response, in particular on the function of CD8 T cells as the crucial players in clearance of virus infected hepatocytes.

We established high fat induced obesity in transgenic mouse models with hepatocyte specific expression of a model antigen (Ova). We investigated the immune response upon adoptive transfer of antigen specific T cells and in mice with continuous thymic output of antigen specific T cells, mimicking the situations upon acute infection and autoimmunity, respectively.

Irrespective of the metabolic condition, adoptive T cell transfer resulted in a transient hepatitis with no obvious differences concerning the acute T cell response. In the situation of autoimmunity, we observed a transient hepatitis in lean mice, whereas an extended hepatitis with a reduced antigen clearance capacity was found in obese mice.

Our results demonstrate that obesity affects T cell function and increases the severity of autoimmune hepatitis while it has no impact on the acute T cell response.