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 prov...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research
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