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Estrogen potentiates treatment with T-cell receptor protein of female mice with experimental encephalomyelitis
Halina Offner, … , Alex Zamora, Arthur A. Vandenbark
Halina Offner, … , Alex Zamora, Arthur A. Vandenbark
Published May 15, 2000
Citation Information: J Clin Invest. 2000;105(10):1465-1472. https://doi.org/10.1172/JCI9213.
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Article

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

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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.

Authors

Halina Offner, Kirsten Adlard, Alex Zamora, Arthur A. Vandenbark

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Figure 1

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Protection of male but not female BV8S2 Tg mice with BV8S2 protein. Litt...
Protection of male but not female BV8S2 Tg mice with BV8S2 protein. Littermate males (a and b) or females (c and d) were treated with saline/IFA or GST/IFA (controls) or 12.5 μg BV8S2 protein/IFA on days –7 and +3 relative to challenge with MBP-Ac1-11 peptide/CFA + pertussigen to induce EAE, with (b and d) or without (a and c) weekly boosting with 12.5 μg BV8S2 protein injected subcutaneously in saline. Note nearly complete protection against EAE in boosted males and delayed onset but eventual development of severe EAE in boosted females. Data from male mice are taken from ref. 19.

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