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Differential effects on T-cell function following exposure to serum from schizophrenia smokers

Molecular Psychiatry volume 15, pages 364–371 (2010)Cite this article

A Corrigendum to this article was published on 18 November 2009

Abstract

Cigarette smoking is more prevalent in subjects with schizophrenia compared to those with other psychiatric disorders or the general population and could therefore affect molecular pathways that impact the pathophysiology of this disorder. As smoking is also known to suppress immune responses, we investigated the effects of ‘smoking-conditioned’ serum obtained from schizophrenia and control subjects on healthy T cell in vitro. We found that T-cell proliferation was significantly increased following exposure to serum from smoking schizophrenia patients whereas no effect was observed when using serum from smoking control subjects or non-smoking patients and controls. We eliminated the possibility that these effects were due to quantitative differences in cigarette consumption as serum levels of the stable nicotine metabolite cotinine were similar in schizophrenic and control smokers. Molecular characterization showed that serum from patient smokers increased expression of T-cell activation markers CD69high, CD25high, co-stimulatory molecules CD26+, CD27+ and CD28+, and decreased T-cell receptor complex components TCRα/β and CD3. Moreover, analysis of supernatants collected after T-cell exposure to serum from smoking patients showed a time-dependent decline in interleukin (IL)-2 levels, suggesting that the proliferation effect is promoted by enhanced IL-2 processing. These results suggest that cigarette smoking has selective effects on serum components that, in turn, lead to altered immune function in schizophrenia patients relative to healthy subjects. Further studies aimed at characterizing these components could result in a better understanding of the onset and aetiology of schizophrenia and potentially lead to novel therapeutic strategies.

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Acknowledgements

We acknowledge all volunteer patient and control blood donors. We thank Nigel Miller and Prof Anne Cooke, Department of Pathology, University of Cambridge for their intellectual input and helpful advice. We also thank Prof Chris Lowe, director of Institute of Biotechnology, University of Cambridge and all members of the Bahn Laboratory for helpful discussions. We are grateful to Dr Fuller Torry (Stanley Medical Research Institute, SMRI) for constructive help with the paper. This research was supported by SMRI and the National Alliance for Research into Schizophrenia and Depression (NARSAD). SB is a NARSAD Essel Investigator. MH is supported by the Cambridge European Trust.

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Authors and Affiliations

  1. Institute of Biotechnology, University of Cambridge, Cambridge, UK

    M Herberth, D N Krzyszton, M R Craddock, E Bulger, E Schwarz, P Guest & S Bahn

  2. Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany

    D Koethe & F M Leweke

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  1. M Herberth
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Correspondence to S Bahn.

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Herberth, M., Krzyszton, D., Koethe, D. et al. Differential effects on T-cell function following exposure to serum from schizophrenia smokers. Mol Psychiatry 15, 364–371 (2010). https://doi.org/10.1038/mp.2008.120

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