1,25=Dihydroxyvitamin D3 and the Immune System (42915)

he recent discovery of receptors for 1,25-dihy-droxyvitamin D3 (1,25-(OH),D3) in cells of the T immune system along with evidence for a mul-tifaceted influence of this hormone on monocytes and lymphocytes have raised the possibility that 1,25-(OH)2D3 is an immunoregulatory agent. The mecha-nism(s) underlying the involvement of 1,25-(OH)2D3 in immunoregulation and the importance of such an in-volvement for physiology, pathophysiology, and thera-peutics, however, remain unclear. The following is an interpretive update of the evi-dence for the interactions between l,25-(OH)2D3 and the immune system. Receptors for 1,25-(OH)*D3 in cells of the immune system It has been well established during the last few years that cells of the hematolymphopoietic tissue are targets for the actions of 1,25-(OH)2D3. Indeed, trans-formed cell lines of the myelomonocytic and the lym-phocytic cell lineage, as well as peripheral normal hu-man blood monocytes and tissue macrophages possess proteins, that, similar to the receptor protein in the classical target tissues of 1,25-(OH)2D3, bind the ligand with high affinity (Kd = lo-' ' M) and specificity and are capable of DNA interactions (1-3). Unlike periph-eral blood monocytes, that express this protein consti-tutively, normal resting T and B lymphocytes do not exhibit detectable binding to radioactive 1,25-(OH)2D3. Nevertheless, activation of peripheral blood T lympho-cytes in vitro with mitogenic lectins, phorbol esters, or antigens leads to the expression of the receptor protein (1, 2, 4). The two major subpopulations of T lympho-cytes, namely, the helper/inducer and suppressor/cy-totoxic cells possess similar concentrations of the 1,25-(OH)2D3 receptor protein upon activation with mito-gens (5). 1,25-(OH)2D3 receptor binding is also present in peripheral blood B lymphocytes activated with the Epstein-Barr virus as well as in myeloma cells (3, 6). The expression of the 1,25-(OH)zD3 receptor in lym-phocytes coincides with the cell entry into the GI