Mild cold stress resulting from standard housing conditions for laboratory mice influences baseline dendritic cell properties (TUM2P.896)

Abstract

Abstract The ability of dendritic cells (DC) to stimulate and regulate T cells is critical for effective anti-tumor immunity. Therefore, it is important to recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice which are commonly used to model anti-tumor immunity. Recent data shows that CD8+ T cell frequency within the tumor microenvironment and anti-tumor function is dependent upon the ambient temperature used to house laboratory mice. As DC function is crucial for CD8+ T cell activation, we hypothesized that DC function is also dependent upon housing temperature. We observed increased numbers of splenic DCs (CD11c+ ) in tumor-bearing mice at housed at standard temperature (ST; 22°C) vs. mice housed at a thermoneutral temperature (TT; 30°C) which alleviates the mild cold stress experienced at ST. Despite increased frequency, DCs from mice at ST primarily display immature phenotypes (MHC II+CD86- ), likely rendering them tolerogenic and unable to activate T cells. Further, splenocytes from tumor-bearing mice at ST were unable to induce T cell proliferation following tumor inoculation while DCs from mice at TT elicited T cell activation. These findings likely contribute to faster tumor growth observed in mice at ST vs. TT. This data strongly suggests that the housing temperature can affect fundamental properties of DC function which in turn influence the ability of DCs to regulate the anti-tumor immune response.