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T-cell Numbers and Antigen-specific T-cell Function Follow Different Circadian Rhythms

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Abstract

Purpose

Circadian rhythms play an important role in modulating cellular immune responses. The present study was performed to characterise circadian variations in lymphocyte numbers and antigen-specific T-cell functionality in healthy individuals under physiological conditions.

Methods

Blood leukocyte populations of six healthy volunteers were quantified over 24 h. In addition, antigen-specific T-cell functionality was analysed directly ex vivo from whole blood using flow cytometry based on intracellular cytokine induction after a 6-hour stimulation with adenovirus antigen and Staphylococcus aureus enterotoxin B (SEB), respectively.

Results

T-cell numbers and reactivity were stable during daytime, whereas a significant increase was observed during late evening and early morning hours. The percentage of T cells reacting towards adenovirus antigen and SEB showed a 1.76 ± 0.55-fold (p = 0.0002) and a 1.42 ± 0.33-fold (p = 0.0002) increase, respectively. Dynamics in T-cell reactivity were independent of the mode of antigen stimulation and inversely correlated with plasma levels of endogenous cortisol. Interestingly, peak frequencies of reactive T cells occurred late in the evening and did not directly coincide with peak numbers of bulk T cells that were observed in the early morning hours.

Conclusions

Taken together, our data reveal a circadian regulation of T-cell immune responses in the peripheral blood of humans under physiological conditions. This knowledge may be of practical consequence for the timing of blood sampling for functional T-cell assays as well as for immunosuppressive drug intake after organ transplantation, where T-cell function may be influenced not only by drug-mediated inhibition but also by circadian fluctuations in T-cell reactivity.

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Acknowledgements

We thank Candida Guckelmus for expert technical assistance, Dr. M. Erhard (Department of Gastroenterology, Saarland University) for help in performing cortisol analyses, and Dr. M. Enders (Labor Enders & Partners, Stuttgart, Germany) for performing serological analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Author notes

  1. Stephan Thijssen

    Present address: Renal Research Institute, New York, USA

Authors and Affiliations

  1. Department of Internal Medicine IV, Saarland University, Homburg, Germany

    Sarah Kirsch, Gunnar H. Heine, Danilo Fliser & Urban Sester

  2. Department of Transplant and Infection Immunology, Institute of Virology, Saarland University, 66421, Homburg, Germany

    Stephan Thijssen, Susana Alarcon Salvador, Kai van Bentum & Martina Sester

Authors
  1. Sarah Kirsch
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  2. Stephan Thijssen
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  3. Susana Alarcon Salvador
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  7. Martina Sester
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Correspondence to Martina Sester.

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Kirsch, S., Thijssen, S., Alarcon Salvador, S. et al. T-cell Numbers and Antigen-specific T-cell Function Follow Different Circadian Rhythms. J Clin Immunol 32, 1381–1389 (2012). https://doi.org/10.1007/s10875-012-9730-z

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  • DOI: https://doi.org/10.1007/s10875-012-9730-z

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