1 Alpha,25-dihydroxyvitamin D3 receptor distribution and effects in subpopulations of normal human T lymphocytes.
Receptors for 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] are expressed upon activation of human lymphocytes, and the hormone inhibits in vitro the proliferation of mitogen-activated lymphocytes. In this study we examined the distribution of the 1,25-(OH)2D3 receptor protein in the two major subsets of T lymphocytes (T helper and T suppressor cells) and the effect of the hormone on their respective rates of proliferation. We activated normal lymphocytes in the presence of monocytes with phytohemagglutinin and subsequently isolated the T helper (T4-positive) and the T suppressor (T8-positive) subsets using monoclonal antibodies and complement-mediated lysis. In parallel experiments, we first isolated monocyte-depleted T4 and T8 cells and then activated them using phytohemagglutinin and a phorbol ester. Using either approach we found that both T4 and T8 lymphocytes expressed the 1,25-(OH)2D3 receptor protein upon activation. The concentration of this protein, its affinity for the ligand (Kd, approximately 10(-10) mol/L), and its sedimentation characteristics (S = 3.3) were indistinguishable in the two T cell subsets. Furthermore, the time kinetics of expression of the receptor after activation were very similar in the two subsets. Nevertheless, 1,25-(OH)2D3 inhibited in a dose-dependent fashion the rate of proliferation of the helper subset, but had no effect on the proliferation of suppressor cells. The finding of a dissimilar effect of 1,25-(OH)2D3 on the proliferation of the T helper and T suppressor cells despite their indistinguishable receptor status suggests that the 1,25-(OH)2D3 receptors of the T cells might not be involved in the effects of the hormone on T-cell proliferation, and that the 1,25-(OH)2D3-induced inhibition of mitogen-activated T4 cell proliferation could be mediated indirectly.
Provvedini
D M
DM
Section of Endocrinology and Metabolism, Veterans Administration Medical Center, Indianapolis, Indiana 46202.
Manolagas
S C
SC
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D010703:Phorbol Esters; D010835:Phytohemagglutinins; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol