title: Amelioration of experimental autoimmune encephalomyelitis by clozapine is not associated with defective CD4 T cell responses.
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.
authors.affiliation: Centre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, P.O. Box 600, Wellington, 6140, New Zealand.
authors.forename: Pirooz
authors.initials: P
authors.lastname: Zareie
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, University of Auckland, Auckland, New Zealand.
authors.forename: Bronwen
authors.initials: B
authors.lastname: Connor
authors.affiliation: Centre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, P.O. Box 600, Wellington, 6140, New Zealand. anne.laflamme@vuw.ac.nz.|The Malaghan Institute of Medical Research, Wellington, New Zealand. anne.laflamme@vuw.ac.nz.
authors.forename: Anne Camille
authors.initials: AC
authors.lastname: La Flamme
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Atypical antipsychotics; EAE; MS; Neuroinflammation