Circadian rhythm in circulating CD16-positive natural killer (NK) cells in macaque monkeys,implication of plasma cortisol levels

The daily change in both percentage and absolute number of circulating major lymphocyte subset was determined with young Japanese monkeys and rhesus monkeys. The blood sample was collected at four hour-intervals beginning at 16:00 for 24 hours under the condition of applying tethering system by which blood samples could be collected without restraint. During the dark period (from 20:00 to 08:00), the number of peripheral lymphocytes increased and that of granulocytes decreased, resulting in no significant change in the number of total peripheral white blood cells. The absolute number of CD4+ T, CD8+ T, and CD20+ B cells showed the significant daily change similar to that in number of peripheral lymphocytes, indicating no proportional change in these subsets. The typical proportional change was observed in CD16+ natural killer (NK) cells and the percentage of CD16+ cells decreased during dark period (from 20:00 to 04:00) and increased in the morning (from 08:00 to 12:00). The NK activity determined by killing K562 target cells showed the same changing pattern as that of percentage in CD16+ NK cells. The changing pattern of both percentage and activity of NK cells was consistent with that of plasma cortisol levels. In addition, the intravenous injection of 300 g/kg of cortisol induced increase in plasma cortisol levels and decrease in percentage of CD16+ NK cells during the first 60 min after cortisol injection. These results strongly suggest that the levels of peripheral functional CD16+ NK cells might be directly regulated by plasma cortisol level in macaque monkeys.