Estrogen potentiates treatment with T-cell receptor protein of female mice with experimental encephalomyelitis.
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-gamma 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-beta. 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.
Offner
H
H
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, Oregon 97201, USA. offner.halina@portland.va.gov
Adlard
K
K
Zamora
A
A
Vandenbark
A A
AA
D000818:Animals; D004357:Drug Synergism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage*; D012727:Sex Characteristics; D014611:Vaccination
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C405722:myelin basic protein 1-11; D004958:Estradiol