Previous recent data reveal that mild heating in vitro of CD4+ and CD8+ T cells (purified from murine splenocytes) at 39.5°C induces the aggregation of lipid rafts; approximately 70% of lymphocytes express aggregated lipid rafts compared to only 20% of cells maintained at 37oC as judged by the distribution of the lipid raft marker, fluorescently labeled GM1. Further, we found that the fluidity of the T cell plasma membrane, as measured by fluorescence anisotropy of TMA-DPH, increases when the temperature is raised from 37° to 39.5°C. Based on these in vitro results, we hypothesized that a physiologically relevant increase in body temperature results in an increase in lipid raft aggregation in T cells in situ. We administered whole body hyperthermia (WBH) to raise the temperature of mice to 39.5°C for 6 hours and immediately harvested and fixed cells from spleen and lymph nodes. Utilizing Imagestream flow cytometry, we observed a 3 fold increase in the number of CD8+ T cells with lipid raft aggregates isolated from WBH mice compared to T cells isolated from normothermic control mice. Lymphocytes from spleen and lymph nodes responded similarly to WBH. Overall, these findings may help to understand the role of physiological temperature shifts (e.g., during febrile episodes and inflammation) on costimulation and lymphocyte activation potential.

Supported by NIH P01 CA94045 and RO1 CA71599