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

Ting Jia, Annandurai Anandhan, Chandirasegaran Massilamany, Rajkumar A. Rajasekaran, Rodrigo Franco-Cruz, N R Jayagopala Reddy

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)620-634
Number of pages15
JournalJournal of Neuroimmune Pharmacology
Volume10
Issue number4
DOIs
StatePublished - Dec 1 2015

Fingerprint

Dihydrotestosterone
Autophagy
Cell Death
T-Lymphocytes
Proteolipids
Autoimmune Experimental Encephalomyelitis
Cytokines
Antigens
Therapeutic Uses
Major Histocompatibility Complex
Paralysis
Androgens
Proteins

Keywords

  • Apoptosis
  • Autophagy
  • Autoreactive T cells
  • DHT
  • MHC class II dextramers
  • Myelin proteolipid protein

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in Autoreactive T Cells Independent of Antigenic Stimulation. / Jia, Ting; Anandhan, Annandurai; Massilamany, Chandirasegaran; Rajasekaran, Rajkumar A.; Franco-Cruz, Rodrigo; Reddy, N R Jayagopala.

In: Journal of Neuroimmune Pharmacology, Vol. 10, No. 4, 01.12.2015, p. 620-634.

Research output: Contribution to journalArticle

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