Stimulation of PIP2 hydrolysis by aluminum fluoride in resting T cell subsets of normal and autoimmune-prone lpr mice.
T cells of autoimmune-prone mice homozygous for the lpr mutation respond poorly to mitogens in terms of proliferation and of IL-2 production. In a previous study, we have correlated this deficient activation with the inability of mitogens to stimulate hydrolysis of phosphatidylinositol 4,5-bisphosphate in lpr T cells, although these cells bind mitogen and express the TCR/CD3 complex. In order to determine whether activation-deficient lpr T cells contain functional GTP-binding (G) protein(s) and phospholipase C, we examined the effects of the G protein activating agent sodium fluoride plus Al+3 (AlF-4). AlF-4 stimulated phosphatidylinositol turnover, a response characteristic of TCR/CD3 occupancy, in mature L3T4+ and Ly2+ T cells. Second, and more important, AlF-4 stimulated the same biochemical events in L3T4-, Ly2- (double-negative) T cells from the normal thymus or from the enlarged lymph nodes of autoimmune-prone mice homozygous for the lpr mutation. However, these double-negative T cells were unresponsive to receptor-active ligands such as T cell mitogens or anti-CD3-epsilon mAb, despite their ability to bind these ligands. These findings suggest that activation-deficient double negative T cells express the receptors, G protein(s) and effector enzymes necessary for second messenger formation and further suggest that the failure of these cells to generate the relevant second messengers in response to mitogens or anti-CD3-epsilon antibody may be due to inefficient coupling of the TCR/CD3 complex to G proteins.
Coggeshall
K M
KM
Scripps Clinic and Research Foundation, Department of Immunology, La Jolla, CA 92037.
Altman
A
A
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005459:Fluorides / Q000494:pharmacology*; D006868:Hydrolysis; D007113:Immunity, Innate; D007399:Interphase / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010641:Phenotype; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D013601:T-Lymphocytes / Q000145:classification / Q000378:metabolism* / Q000502:physiology
D017607:Aluminum Compounds; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D000535:Aluminum; D005459:Fluorides; C032311:aluminum fluoride