Mild Hyperthermia Modulates the Relative Frequency of Lymphocyte Cell Subpopulations : an Increase in a Cytolytic NK Cell Subset and a Decrease in a Regulatory T Cell Subset

Abstract

Although mild hyperthermia (MHT) cannot directly kill tumor cells, an augmented immunological effect resulting from MHT has been reported to induce injury of malignant tumors. In this study, the impact of regional MHT on lymphocyte subpopulations was investigated. Of particular interest was the effect of MHT on natural killer (NK) cells and T cells, which are important in the innate and adaptive immune systems. Regional MHT treatment was performed using an 8-MHz capacitive heating device, the Thermotron RF8 (Yamamoto Vinita Co., Ltd., Osaka, Japan). An average continuous radio-frequency irradiation of approximately 900 W was applied between two 30-cm electrodes placed on opposite sides of a volunteer's upper abdominal region for 30 min. In healthy volunteers exposed to this thermal treatment, NK cell activity and the percentage of NK cells and cytolytic NK cells (CD3^-CD56^dim cells) in lymphocyte populations increased significantly at 1 and 7 days after regional MHT treatment compared with pre-treatment numbers. The number of cytolytic NK cells also increased significantly at 1 day after treatment. The percentage of T cells and CD4⁺ T cells decreased significantly from 1 to 7 days following the heating procedure. However, no significant changes in the percentage and the number of CD8⁺ T cells was observed. Interestingly, the percentage and the number of CD4⁺CD25⁺ T lymphocytes which are recognized as regulatory T lymphocytes (T_reg) decreased significantly during the 7 day post-treatment period. These results suggest that regional MHT may activate both, the innate and adaptive immune systems, through activation of NK cells and through a decrease in the number of regulatory T cells.