Regulatory T cells mediate immunosupression induced by experimental hypothyroidism

VALLI E; STERLE H A; MÉNDEZ HUERGO S; MASCANFRONI ID; KLECHA AJ; BARREIRO ARCOS ML; RABINOVICH G; CREMASCHI GA

Honolulu

Congreso; Immunology 2013, American Association of Immunologists Annual Meeting; 2013

American Association of Immunologist (AAI)

Thyroid status modulates immunity, being the circulating levels of thyroid hormones (THs) responsible for the regulation of lymphocyte activity. Formerly we observed that experimental hypothyroidism (Exp-hypo) decreases Th1 cytokine production and T cell-mediated immunity. Here we aimed to elucidate the mechanisms underlying immunosuppression triggered by Exp-hypo. Lymphocyte subsets were assessed in spleens and lymph nodes of hypothyroid (hypo-WT) and control (C) mice. Percentage of Treg (CD4+CD25+FoxP3+) cells (Tregs %) was significantly increased in the hypo-WT group without differences in CD3/CD19 or CD4/CD8 ratios. When naïve T cells were differentiated to inducible Treg cells in vitro, similar results were obtained. Treg cells overexpress galectin-1 (Gal-1), an immunoregulatory β-galactoside-binding protein, and mice lacking this lectin (Lgals1-/-) showed reduced Treg cell activity. To evaluate the role of Gal-1 in the regulation of Tregs in Exp-hypo we also analyzed lymphocyte reactivity and the percentage of Tregs % in eu- and hypothyroid Lgals1-/- mice (hypo-KO). We found an increased T cell proliferation and a reduction in the Tregs % in hypo-KO mice respect to the hypo-WT group. We conclude that modulation of immunity in the Exp-hypo with low circulating levels of THs is associated to a significant rise in the percentage of spontaneous and inducible Tregs. This increase relies on the expression of Gal-1 and may be related to a functional deficit of T cells.