Impaired T-cell activation in patients with systemic lupus erythematosus.
Interleukin-2 (IL-2) production was studied in T lymphocytes from 32 patients with systemic lupus erythematosus (SLE) and 27 healthy volunteers. The IL-2 production by phytohemagglutinin (PHA)-stimulated cells from SLE patients was significantly depressed compared to control values, with a correlation between degree of depression and disease activity. The depressed IL-2 production by SLE T cells are largely reversed by the addition of either phorbol ester (PMA) or partially by a calcium ionophore. SLE T cells had significantly lower peak increases in intracellular free calcium [( Ca2+]i) than controls after stimulation by PHA or by a monoclonal antibody against the CD3 antigen. This abnormality was found even in T cells from patients with mild disease activity or in those whose T cells produced normal amounts of IL-2. Calcium ionophore produced similar increases in [Ca2+]i in SLE patients as in normals. These results suggest that a major component of the defect responsible for decreased IL-2 production by SLE lymphocytes is proximal to protein kinase C activation and may involve impaired signal transduction after activation of the antigen receptor complex.
Sierakowski
S
S
Department of Medicine, University of Wisconsin School of Medicine, Milwaukee.
Kucharz
E J
EJ
Lightfoot
R W
RW
Goodwin
J S
JS
D000328:Adult; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007376:Interleukin-2; D010835:Phytohemagglutinins; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium