Seasonal modulation of the circadian time structure of circulating T and natural killer lymphocyte subsets from healthy subjects.
Open accessAbstract
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.
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However, given low-to-normal total CD4+ and CD8+ T-cells, the apparent decline in memory T-cells could also be explained by the low point of normal T-cell circannual kinetics at the 2-year follow-up.
“However, in light of the low-to-normal total CD4+ and CD8+ T-cells, this apparent decline could also be explained by the low point of normal T-cell circannual kinetics at the 2-year follow-up [44].”
From Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm (2021) · cites this paper as [44]
The Circannual rhythms section reports seasonal variation in OKT8+ T-cell counts and a six-month rhythm in OKT4+ counts, supporting the possibility of normal fluctuations in these populations. The paper studied healthy men, however, and did not measure memory T cells or establish that the cited two-year follow-up fell at a seasonal low point. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOver 2 years, T-cell subsets displayed circannual kinetics, especially in the CD25+/CD28+ subsets incorporating Tregs.
“Over 2 years, T-cell subsets displayed circannual kinetics [44, 45], especially noted in the CD25+/CD28+ subsets, incorporating Tregs.”
From Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm (2021) · cites this paper as [44]
The Circannual rhythms section reports annual rhythms in OKT3+ and OKT8+ T-cell subsets; the Discussion notes that some individuals were studied in the preceding year. However, the Lymphocyte surface marker determinations section lists OKT3, OKT4, OKT8, and HNK-1—not CD25 or CD28—and the paper does not identify a Treg subset or find rhythms especially in one. Page numbers were not available in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measured
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- Authors
- Lévi, F. A., Canon, C., Touitou, Y., Reinberg, A., & Mathé, G.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Pitié-Salpêtrière Hospital (FR)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1988-02-01
- Volume
- 81
- Issue
- 2
- Pages
- 407-413
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC329583
- OpenAlex
- W1964130172
- Cited by
- 104
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 1 · 2015: 1 · 2014: 4 · 2013: 4
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- circadian rhythm, seasonal variation, T cells, natural killer cells, T helper cells, suppressor/cytotoxic T cells, lymphocyte subsets, circannual rhythm, peripheral blood lymphocyte count, healthy men
- MeSH terms
- Adult, Antibodies, Monoclonal, Circadian Rhythm, Humans, Killer Cells, Natural, Leukocyte Count, Male, Seasons, T-Lymphocytes
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