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A seasonal modulation of the circadian time structure of circulating T and natural killer (NK) lymphocyte subtypes was documented in five healthy men aged 24-36 yr. Venous blood was obtained every 4 h for 24 h from each subject in January, March, June, August, and November 1984. Three subjects were also studied in April and/or August and/or November 1983 for the T subsets only. Mononuclear cells were isolated on Ficoll-Paque gradient and aliquots were incubated with OKT3, OKT4, OKT8, or HNK-1 monoclonal antibodies for characterizing all, T, T helper, T suppressor-cytotoxic, and NK lymphocytes, respectively, under an epifluorescence microscope. An effect of both sampling time and study month was statistically validated (P less than 0.01) with both two-way analysis of variance and cosinor for the peripheral counts in total, pan-T, T helper, and NK lymphocytes (cells per cubic millimeter). Seasonal changes affected both the circadian patterns and the 24-h mean values. Thus the double amplitude (total extent of variation) of the circadian rhythm in circulating total, T and T helper lymphocytes varied between 0 in March (P greater than 0.30; no rhythm) and up to 46-68% of the 24-h-mean (M) in November, with acrophases (times of maximum, 0) localized in the first half of the night (P less than 0.001). Maximal values were found at 8:30 h for both T suppressor-cytotoxic and NK lymphocytes; a smaller second peak was also found at 20:30 h, and a 12-h rhythm was validated by cosinor (P less than 0.0001), with no patient change in waveform along the year scale. A circannual rhythm was statistically validated by cosinor for total (0 in November), pan-T (0 in March), T suppressor-cytotoxic (0 in December), and NK lymphocytes (0 in October). A rhythm with a period equal to 6 mo was found for circulating T helper cells with 0 occurring both in April and October. Seasonal variations in the incidence of several immunologically related diseases may correspond to an endogenous circannual time structure.

Seasonal modulation of the circadian time structure of circulating T and natural killer lymphocyte subsets from healthy subjects.