1,25-Dihydroxyvitamin D3 Antagonizes Interferon-γ-Induced Expression of Class II Major Histocompatibility Antigens on Thyroid Follicular and Testicular Leydig Cells*

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Abstract
Interferon-.gamma. (IFN.gamma.) induces production and expression of major histocompatibility complex class II molecules on both marrow-derived and nonbone marrow-derived cell types. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], a seco-steroid derived from vitamin D3, has previously been reported to enhance such expression alone or together with IFN.gamma. on a number of monocyte/macrophage tumorigenic lines. In contrast, the present studies have found that 1,25-(OH)2D3 inhibited the ability of IFN.gamma. to induce class II antigen expression on non-transformed rat thyroid follicular epithelial cells (FRTL-5) and mouse testicular Leydig cells (TM3). Although 1,25-(OH)2D3 inhibited the induction of both IA and IE class II locus products, IFN.gamma. augmentation of class I major histocompatibility complex antigens was not affected. 1,24-(OH)2D3 and 24,25-(OH)2D3 also inhibited class II induction by IFN.gamma.. Notably, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-(OH)2D3 receptor, indicating that this antagonistic effect probably requires receptor-ligand interaction. Other steroid hormones, such as hydrocortisone or testosterone, had no inhibitory effect on IFN.gamma.-induced class II expression on Leydig cells. Additionally, the failure of intomethacin to reverse the effect of 1,25-(OH)2D3 and the finding that exogenous prostaglandin E2 did not inhibit class II induction in these cells indicated that prostaglandins are probably not responsible for this anti-IFN.gamma. activity. In total, these results suggest that an endocrinological mediator is capable of inhibiting class II induction on resident endocrine tissue populations and, therefore, could help to diminish local CD4+ T-cell recognition of these cells.

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