Defective signal transduction in CD4-CD8- T cells of lpr mice.
Mice homozygous for the lpr gene develop a lymphoproliferative disorder due to expansion of a subset of CD4-CD8- T cells. Triggering of the T-cell receptor in these lpr T cells does not lead to translocation of protein kinase C or phosphorylation of CD3, interleukin-2 production, or proliferation, whereas a combination of phorbol ester and calcium ionophore does. Stimulation with concanavalin A or anti-CD3 induces phosphoinositide hydrolysis. The rise in inositol bisphosphate, inositol triphosphate, and inositol tetrakisphosphate, identified by HPLC, is similar in +/+ and lpr T cells. The concentration of cytoplasmic free calcium ([Ca2+]i), however, under basal and stimulated conditions is significantly lower in lpr T cells. The lower basal [Ca2+]i may explain why induction of proliferation with phorbol ester and calcium ionophore requires a higher concentration of ionophore in these cells than in normal T cells. The lower [Ca2+]i obtained on stimulation may contribute to the activation defect of CD4-CD8- lpr T cells.
Stafford-Brady
F
F
Department of Medicine, Massachusetts General Hospital, Boston.
Sugiyama
E
E
Robinson
D R
DR
Sy
M S
MS
Bonventre
J V
JV
Yeh
E T
ET
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D002118:Calcium / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D010716:Phosphatidylinositols / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D000943:Antigens, Differentiation; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D003208:Concanavalin A; D002118:Calcium