1alpha,25-Dihydroxyvitamin D3 modulates CD38 expression on human lymphocytes.

B cells from chronically stimulated tonsils displayed high initial mean 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 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) restored the initial CD38 expression on these stimulated cells and up-regulated the Ag on stimulated CD38-/low cells. 1,25(OH)2D3 enhanced CD38 expression by four- to sixfold on CD8- and CD8+ peripheral blood T cells following PHA activation. The EC50 values for induction were 2 to 3 nM. Although all-trans-retinoic acid also induced CD38 expression on stimulated B and T cells, it was less effective than 1,25(OH)2D3. B cell CD38 expression was augmented less by 1,25(OH)2D3 than by IFN-alpha and IFN-gamma. However, T cell CD38 expression was induced more strongly by 1,25(OH)2D3 than by IFN-alpha, and was unaffected by IFN-gamma. The CD38 density on activated 1,25(OH)2D3-treated CD38-/low B and peripheral T cells was proportional to cell size, indicating that hormonal induction depended upon entry into the cell cycle. While IFNs induced CD38 rapidly in stimulated T and B lymphocytes, 1,25(OH)2D3 exerted its effects only after initial 1- to 3-day delays, suggesting a requirement for nuclear 1,25(OH)2D3 receptor up-regulation. In HL-60 cells, which constitutively express the nuclear receptors, 1,25(OH)2D3 rapidly induced CD38 Ag and ectoenzyme activity. The CD38 density on freshly isolated unfractionated tonsillar B lymphocytes and on the activated 1,25(OH)2D3-treated cultured cells was nearly identical for cells within the same size range, indicating that in vitro hormonal exposure reconstituted in vivo CD38 expression levels.