Fever-range hyperthermia stimulates L-selectin–dependent and α4β7 integrin–dependent migration of lymphocytes to LN and PP.

The 300.19/L-selectin cells and TK1 cells were cultured at 37°C or treated for 6 hours in vitro with fever-like hyperthermia (Cell/HT; 40°C), and then labeled with PKH-26 fluorescent dye. PKH-26–labeled cells were mixed with equivalent numbers of FITC-labeled internal standard cells (300.19/L-Δcyto cells or TK1 cells treated with DATK32 mAb) and injected intravenously into normothermic control mice (core temperature, 36.8 ± 0.2°C) or mice pretreated with WBH (39.7 ± 0.2°C). After 1 hour, the number of fluorescent cells in single-cell suspensions of lymphoid tissues was determined. Data represent the relative accumulation of cells in lymphoid tissues, expressed as a percentage of control cells (ie, cells of the same type maintained at 37°C) that were labeled identically and injected into normothermic mice. Therefore, 100% in the graph (broken lines) represents the behavior of cells cultured at 37°C after injection into normothermic control mice. Values are the mean ± SE of 3 independent experiments. The difference in accumulation of 300.19/L-selectin cells or TK1 cells relative to internal standard cells (300.19/L-Δcyto cells or DATK32-treated TK1 cells, respectively) was significant by unpaired 2-tailed Student ttest (* indicates P < .0001; and **,P < .005). The SEM for 300.19/L-Δcyto cells and DATK32-treated TK1 cells was less than or equal to 10% (not shown).