Effects of TX527, a hypocalcemic vitamin D analog on human activated T lymphocytes

Hypocalcemic vitamin D analogs are appealing molecules to exploit the immunomodulatory actions of active vitamin D in vivo. The functional modulation of dendritic cells is regarded as the key mechanism underlying their ability to regulate T cell responses. In contrast, the direct actions of vitamin D and structural analogs on T lymphocytes remain less well characterized. Microarray analysis was performed to gain insight into the direct immunomodulatory actions of TX527, a hypocalcemic vitamin D analog, on human T lymphocytes. Gene expression analysis revealed that TX527 regulated a wide variety of genes involved in different aspects of T cell function, including cellular growth and proliferation, cell death, cellular development, cellular movement and cell-to-cell signalling and interaction. Human CD3+ T cells, isolated from peripheral blood from healthy donors, were activated by anti-CD3/anti-CD28 and cultured in the presence of TX527 (10-8M) or vehicle (ethanol) for 10 days. Expression profiles of TX527-treated and vehicle-treated T cells were compared using Affymetrix Human Genome U133 Plus 2.0 Arrays.