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.
Stoeckler
J D
JD
Department of Pathology, Roger Williams Medical Center and Brown University, Providence, RI 02908, USA.
Stoeckler
H A
HA
Kouttab
N
N
Maizel
A L
AL
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D002117:Calcitriol / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D009244:NAD+ Nucleosidase / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D014212:Tretinoin; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D002117:Calcitriol