Characterization of the interference of T cell activation by reserpine.
It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) reactions by depleting tissue mast cells of serotonin, thereby preventing a T cell-dependent release of mast cell serotonin necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. Recently, we showed that the ability of reserpine to interfere with the expression of contact sensitivity was independent of an effect on mast cells, but reflected an effort of the drug on effector T cell function. In the present study we evaluated the mechanisms by which reserpine abrogates the expression of T cell functions. By using human peripheral blood mononuclear cells or enriched T cell populations we found that the drug inhibited, in a dose-dependent fashion, the proliferation of T cells after mitogen stimulation. Reserpine also interfered with the mitogen-induced IL-2 production by these cells, but the IL-2 receptor expression, as measured by immunofluorescence, was unaffected. Despite this, in the continuous presence of reserpine, exogenous IL-2 did not bypass reserpine inhibition of PHA-induced proliferation. By using the fluorescent indicator quin-2 we have demonstrated that preincubation with reserpine prevented the increase of cytosolic free calcium, which accompanies PHA-induced proliferative responses of human T lymphocytes. These results identify the sites of action of reserpine in human T lymphocytes and are sufficient to explain its ability to block cell-mediated immune responses in vitro and in vivo.
Mekori
Y A
YA
Allergy-Immunology Unit, Meir Hospital, Kfar Saba, Israel.
Blickstein
D
D
Baram
D
D
Alter
A
A
Radnay
J
J
Rozenszajn
L A
LA
Ravid
M
M
D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D000001:Calcimycin; C033170:4-bromo-A-23187; D012110:Reserpine; D002118:Calcium