title: Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation.
abstract: Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139-151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT induced cell death in antigen-specific, autoreactive T cells, but the effects were not selective, because both proliferating and non-proliferating cells were equally affected independent of antigenic stimulation. Furthermore, DHT-exposed PLP 139-151-specific T cells did not show any shift in cytokine production; rather, frequencies of cytokine-producing PLP-specific T cells were significantly reduced, irrespective of T helper (Th) 1, Th2, and Th17 subsets of cytokines. By evaluating cell death and autophagy pathways, we provide evidence for the induction of autophagy to be associated with cell death caused by DHT. Taken together, the data provide new insights into the role of DHT and indicate that cell death and autophagy contribute to the therapeutic effects of androgens in autoreactive T cells.
authors.affiliation: Room 202, Bldg. VBS, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Jia
authors.affiliation: Room 202, Bldg. VBS, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.
authors.forename: Annandurai
authors.initials: A
authors.lastname: Anandhan
authors.affiliation: Room 202, Bldg. VBS, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.
authors.forename: Chandirasegaran
authors.initials: C
authors.lastname: Massilamany
authors.affiliation: Room 202, Bldg. VBS, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.
authors.forename: Rajkumar A
authors.initials: RA
authors.lastname: Rajasekaran
authors.affiliation: Room 202, Bldg. VBS, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Franco
authors.affiliation: Room 202, Bldg. VBS, School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA. nreddy2@unl.edu.
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D016207:Cytokines / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects
chemical_list: D000728:Androgens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D013196:Dihydrotestosterone
keywords: Apoptosis; Autophagy; Autoreactive T cells; DHT; MHC class II dextramers; Myelin proteolipid protein