Immune regulatory properties of corticosteroids: prednisone induces apoptosis of human T lymphocytes following the CD3 down-regulation.
Glucocorticoid hormones (GCH) induce apoptosis in PHA-primed peripheral blood T lymphocytes (PBL) and down-regulate membrane-bound proteins involved in the immune response. We have analyzed whether GCH are able to affect the expression of the TCR-associated molecules CD3, CD4, and CD8 on PBL-PHA, and whether the modulation of those receptors is related to the GCH-driven apoptosis of the PBL-PHA. Lymphocytes were cultured with PHA or with PHA plus prednisone (PDN) 10(-3), 10(-6), and 10(-9) M. Then expression of CD2, CD3, CD4, CD8, and CD56 antigens was studied by cytofluorimetric assay using propidium iodide (PI) staining and annexin procedure, and by gel electrophoresis of low molecular weight DNA. PDN, at a pharmacological concentration (10(-6) M), was able to inhibit the CD3 expression on T cells. The kinetics of CD3 decrement and of apoptosis show that the down-regulation of CD3 molecules precedes DNA fragmentation and that the cells lacking CD3 are those prone to PDN-induced apoptosis. The inhibition of CD3 is not related to a transcriptional or posttranscriptional phenomenon, because both PBL-PHA and PBL-PHA-PDN expressed the same amount of intracytoplasmic CD3 molecule. PDN also induced a down-regulation of the CD4 and CD8 molecules that resulted sooner in more intense CD8. In vitro PDN is able to induce apoptosis in PBL-PHA through a down-regulation of CD3 molecules.
Department of Internal Medicine (DI.M.I), University of Genova, Italy.
M
M
Scudeletti
L
L
Lanza
E
E
Monaco
M
M
Monetti
F
F
Puppo
G
G
Filaci
F
F
Indiveri
D000305:Adrenal Cortex Hormones / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D017252:CD3 Complex / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007107:Immune System / Q000502:physiology*; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology; D011241:Prednisone / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
D000305:Adrenal Cortex Hormones; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D005938:Glucocorticoids; D010835:Phytohemagglutinins; D011241:Prednisone