EFFECT OF 1,25-DIHYDROXYVITAMIN D-3 ON MOUSE THYMUS - ROLE OF EXTRACELLULAR CALCIUM

We recently reported that mice treated with 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) or 19-nor-1,25-(OH)(2)D-2 experienced a severe loss of their thymocytes and decreased proliferation in response to concana valin A mitogen. The present study investigated the effect of short-te rm treatment with 1,25-(OH)(2)D-3 on the thymic architecture and thymo cyte subsets. Daily treatment with 1,25-dihydroxyvitamin D-3 at 20 ng per mouse for 4 days induced significant involution of thymic tissue. The atrophy was predominantly observed in the cortical component. Flow cytometric analysis of thymocyte subsets showed that the CD4 + CD8 population was the primary target. Since the treated mice experienced profound hypercalcemia, we studied the effect of 1,25-(OH)(2)D-3 on an imals fed a vitamin D-deficient, low calcium diet or the same diet con taining vitamin D for 25 days prior to treatment. The low calcium fed mice showed severe hypocalcemia and slight thinning of thymic cortex. Treatment with 1,25-(OH)(2)D-3 moderately improved the hypocalcemia bu t had no further effect on the thymus of these animals. On the other h and, hypercalcemia and thymic atrophy were found in the animals fed th e diet containing vitamin D. Overall, the atrophy effect on the thymus caused by 1,25-(OH)(2)D-3 treatment was prevented by eliminating the hypercalcemia observed in + D + Ca treated animals. Thus, thymic atrop hy probably resulted from hypercalcemia and not from 1,25-(OH)(2)D-3 i tself.