1-ALPHA,25-DIKYDROXYVITAMIN D-3 MODULATES CD38 EXPRESSION ON HUMAN-LYMPHOCYTES

B cells from chronically stimulated tonsils displayed high initial mea n CD38 levels that declined during in vitro culture, despite ligation of CD40 and/or the Ag receptor in the presence of IL-4. Exposure to 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) restored the initial CD 38 expression on these stimulated cells and up-regulated the Ag on sti mulated CD38(-/low) cells, 1,25(OH)(2)D-3 enhanced CD38 expression by four- to sixfold on CD8(-) and CD8(+) peripheral blood T cells followi ng PHA activation, The EC(50) values for induction were 2 to 3 nM. Alt hough all-trans-retinoic acid also induced CD38 expression on stimulat ed B and T cells, it was less effective than 1,25(OH)(2)D-3. B cell CD 38 expression was augmented less by 1,25(OH)(2)D-3 than by IFN-alpha a nd IFN-gamma. However, T cell CD38 expression was induced more strongl y by 2,25(OH)(2)D-3 than by IFN-alpha, and was unaffected by IFN-gamma . The CD38 density on activated 1,25(OH)(2)D-3-treated CD38(-/low) B a nd peripheral T cells was proportional to cell sit, indicating that ho rmonal induction depended upon entry into the cell cycle, While IFNs i nduced CD38 rapidly in stimulated T and B lymphocytes, 1,25(OH)(2)D-3 exerted its effects only after initial 1- to 3-day delays, suggesting a requirement for nuclear 1,25(OH)(2)D-3 receptor up-regulation, In HL -60 cells, which constitutively express the nuclear receptors, 2,25(OH )(2)D-3 rapidly induced CD38 Ag and ectoenzyme activity. The CD38 dens ity on freshly isolated unfractionated tonsillar B lymphocytes and on the activated 1,25(OH)(2)D-3-treated cultured cells was nearly identic al for cells within the same size range,indicating that in vitro hormo nal exposure reconstituted in vivo CD38 expression levels.