Skip to main content
main-content

01.12.2017 | Short report | Ausgabe 1/2017 Open Access

Journal of Neuroinflammation 1/2017

Amelioration of experimental autoimmune encephalomyelitis by clozapine is not associated with defective CD4 T cell responses

Zeitschrift:
Journal of Neuroinflammation > Ausgabe 1/2017
Autoren:
Pirooz Zareie, Bronwen Connor, Anne Camille La Flamme
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12974-017-0842-5) contains supplementary material, which is available to authorized users.

Abstract

Atypical antipsychotic agents, such as clozapine, are used for treating psychosis and depression and have recently been found to modulate neuroinflammation. We have shown previously that treatment of mice with the atypical antipsychotic agents, clozapine or risperidone, attenuates disease severity in experimental autoimmune encephalomyelitis (EAE); however, the mechanism by which they are protective is unknown. In this study, we investigated the effects of clozapine on CD4+ T cell responses and found that clozapine did not significantly affect the expansion of myelin-specific T cells, their differentiation into pathogenic subsets, or their encephalitogenic capacity to induce EAE. Interestingly, although clozapine enhanced differentiation of regulatory T (Treg) cells, in vivo neutralization of Tregs indicated that Tregs were not responsible for the protective effects of clozapine during the induction and effector phase of EAE. Taken together, our studies indicate that clozapine does not mediate its protective effects by directly altering CD4 T cells.
Zusatzmaterial
Additional file 1: Gating strategy for identifying dopaminergic and adrenergic receptors on T cells. Spleens were isolated from mice 15 d.p.i and analyzed by flow cytometry for dopamine and adrenergic receptor expression. A gating strategy for identifying CD4 (bottom left), CD8 (bottom center), and Tregs (bottom right). Representative histograms for expression of B dopamine D1 receptor (D1R) and C dopamine D2 receptor (D2R) on CD4 T cells. Graphical representation of receptor expression on different T cell subsets of D D1R and E D2R. Shown are means and SEM of individual mice from one experiment (n = 5 mice in each group). Statistical analyses between healthy control and EAE mice conducted by two-way ANOVA. (TIF 17402 kb)
12974_2017_842_MOESM1_ESM.tif
Additional file 3: Gating strategy to identify CD4+ T cells and 2D2 MOG35-55 TCR CD4+. Single cells were gated using FSC-A and FSC-H. Cells of interest were gated using FSC-A and SSC-A. Lymphocytes were identified by CD11b− and CD3+ expression. CD4 T cells were distinguished using CD8− and CD4+ expression. Tregs were identified as CD25+ and Foxp3+. Th17 cells were identified as ROR\( \gamma \)T+. (TIF 14847 kb)
12974_2017_842_MOESM3_ESM.tif
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2017

Journal of Neuroinflammation 1/2017 Zur Ausgabe

Neu in den Fachgebieten Neurologie und Psychiatrie

Meistgelesene Bücher in der Neurologie & Psychiatrie

  • 2016 | Buch

    Neurologie

    Das Lehrbuch vermittelt Ihnen das gesamte Neurologie-Prüfungswissen für Ihr Medizinstudium und bereitet auch junge Assistenzärzte durch detailliertes Fachwissen optimal auf die Praxis vor. Die komplett überarbeitete Auflage enthält sechs neue, interdisziplinäre Kapitel.

    Herausgeber:
    Werner Hacke
  • 2016 | Buch

    Komplikationen in der Neurologie

    Das Buch schildert Ereignisse im Rahmen der Neuromedizin, die während der Diagnostik und Therapie neurologischer Erkrankungen und Symptome auftreten können. Die Fallbeispiele sensibilisieren Sie für mögliche Risikofaktoren, um das Auftreten solcher Komplikationen zu vermeiden.

    Herausgeber:
    Frank Block
  • 2017 | Buch

    Facharztwissen Psychiatrie, Psychosomatik und Psychotherapie

    Leitsymptome, Untersuchungsmethoden, Krankheitsbilder, Notfälle & Co. – mit der Neuauflage des "Facharztwissens" sind Sie auf die Facharztprüfung in Psychiatrie und Psychotherapie optimal vorbereitet. In dieser 2. Auflage sind die Kapitel zu psychosomatischen Störungen deutlich ausgebaut.

    Herausgeber:
    Prof. Dr. Dr. Frank Schneider
  • 2019 | Buch

    Kompendium der Psychotherapie

    Für Ärzte und Psychologen

    Dieses Werk wendet sich an Ärzte und Psychologen, die an psychiatrischen und psychosomatischen Kliniken oder an Psychotherapeutischen Ausbildungsinstituten arbeiten und in den vorhandenen Lehrbüchern der Psychotherapie den Brückenschlag zur …

    Herausgeber:
    Tilo Kircher