title: Differential effects on T-cell function following exposure to serum from schizophrenia smokers.
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 CD69(high), CD25(high), co-stimulatory molecules CD26+, CD27+ and CD28+, and decreased T-cell receptor complex components TCRalpha/beta 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.
authors.affiliation: Institute of Biotechnology, University of Cambridge, Cambridge CB2 1QT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Herberth
authors.forename: D N
authors.initials: DN
authors.lastname: Krzyszton
authors.forename: D
authors.initials: D
authors.lastname: Koethe
authors.forename: M R
authors.initials: MR
authors.lastname: Craddock
authors.forename: E
authors.initials: E
authors.lastname: Bulger
authors.forename: E
authors.initials: E
authors.lastname: Schwarz
authors.forename: P
authors.initials: P
authors.lastname: Guest
authors.forename: F M
authors.initials: FM
authors.lastname: Leweke
authors.forename: S
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood; D049109:Cell Proliferation; D003367:Cotinine / Q000097:blood; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000097:blood*; D012565:Schizophrenic Psychology; D012907:Smoking / Q000097:blood*; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; D003367:Cotinine