Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation

Authors

Ting Jia, University of Nebraska-LincolnFollow
Annandurai Anandhan, University of Nebraska-LincolnFollow
Chandirasegaran Massilamany, University of Nebraska-LincolnFollow
Rajkumar A. Rajasekaran, University of Nebraska-LincolnFollow
Rodrigo Franco, University of Nebraska-LincolnFollow
Jay Reddy, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2015

Citation

Published in Journal of Neuroimmune Pharmacology 10 (2015), pp. 620–634; doi: 10.1007/s11481-015-9633-x

Comments

Copyright © 2015 Springer Science+Business Media New York. Used by permission.

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.

Includes Supplementary Materials.

An Erratum for this article is attached (below).