Febrile temperatures enhance early T cell activation

Abstract

The immune system is highly sensitive to changes in body temperature. While hyperthermia enhances the immune response (e.g. during fever) [1-3], hypothermia has immuno-suppressive properties that are used in anti-inflammatory treatments [4-5]. Interestingly, the cellular or molecular mechanisms of temperature-induced immuno-modulation are barely understood. We investigated the influence of temperature on the early signalling of primary CD4+ T cells from 5c.c7 TCR-transgenic mice. Functionalized supported lipid bilayers (SLB) mimic the surface of antigen presenting cells and allow for specific activation by supplying the cognate antigen as well as costimulatory and adhesion proteins. Glass substrates with microscopy-compatible heating elements (VAHEAT, Interherence) allow for precise temperature control at the interface between bilayer and T cell. Via ratiometric calcium imaging, we detect activated T cells and show that hyperthermia not only increases T cell sensitivity but also accelerates the activation process. Additionally, we characterize how increased temperatures damage functionalized SLBs and present strategies to maintain bilayer integrity.