Estrogen potentiates treatment with T-cell receptor protein of female mice with experimental encephalomyelitis

Halina Offner, Kirsten Adlard, Alex Zamora, Arthur Vandenbark

Research output: Contribution to journalArticle

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Abstract

Transgenic mice expressing the BV8S2 chain, which is specific for the myelin basic protein determinant Ac1-11, possess a naturally induced set of regulatory T cells directed against BV8S2. Further activation of anti-BV8S2 T cells in male mice with recombinant BV8S2 protein can inhibit IFN-γ release by Ac1-11-specific T cells through a cytokine-driven mechanism and prevent induction of experimental autoimmune encephalomyelitis (EAE). In contrast, naive female mice possess fewer anti-BV8S2-reactive T cells, and treatment with BV8S2 delayed but did not prevent EAE. We here demonstrate that combining T-cell receptor (TCR) vaccination with supplemental estrus doses of estrogen potentiated IL-10 production by anti-BV8S2-reactive T cells and induced Ac1-11-specific T cells to produce IL-10 and TGF-β. This combined treatment resulted in full protection against EAE, which was not observed with either therapy alone. These findings imply that supplemental estrogen can enhance the efficacy of TCR-based immunotherapy for autoimmune diseases that predominate in females.

Original languageEnglish (US)
Pages (from-to)1465-1472
Number of pages8
JournalJournal of Clinical Investigation
Volume105
Issue number10
StatePublished - May 2000

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Encephalomyelitis
T-Cell Antigen Receptor
Estrogens
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Proteins
Interleukin-10
Therapeutics
Estrus
Regulatory T-Lymphocytes
Recombinant Proteins
Immunotherapy
Transgenic Mice
Autoimmune Diseases
Vaccination
Cytokines

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Estrogen potentiates treatment with T-cell receptor protein of female mice with experimental encephalomyelitis. / Offner, Halina; Adlard, Kirsten; Zamora, Alex; Vandenbark, Arthur.

In: Journal of Clinical Investigation, Vol. 105, No. 10, 05.2000, p. 1465-1472.

Research output: Contribution to journalArticle

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