Activation via the antigen receptor is impaired in T cells, but not in B cells from patients with common variable immunodeficiency.
The patients included in this study belong to a subset of common variable immunodeficiency (CVID) patients whose peripheral blood T cells have a T cell receptor (TCR)-mediated activation defect leading to impaired expression of the interleukin (IL)-2 gene upon stimulation with recall antigens (tetanus toxoid, Escherichia coli) or superantigens (staphylococcal enterotoxins). In the present report we demonstrate that the patients' peripheral blood T cells failed to generate the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) following stimulation with superantigen or mAb specific for the monomorphic region of the TCR beta-chain. Patients' T cell lines were also impaired in generating Ins(1,4,5)P3 when stimulated with tetanus toxoid-pulsed autologous monocytes. Addition of a second or third co-stimulatory signal provided by recombinant IL-2, CD28 or both had no effect on the Ins(1,4,5)P3 formation of the patients' antigen-driven T cell lines. The T cell activation defect, however, was not absolute, as Ins(1,4,5)P3 formation in the patients' T cells after phytohemagglutinin or aluminium fluoride stimulation was normal. The impairment in signal transduction via the T cell antigen receptor was limited to the patients' T cells, as no activation defect after ligation of surface immunoglobulin, the antigen receptor on B cells, could be detected.
Fischer
M B
MB
Institute of Immunology, University of Vienna, Austria.
Wolf
H M
HM
Hauber
I
I
Eggenbauer
H
H
Thon
V
V
Sasgary
M
M
Eibl
M M
MM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation; D009000:Monocytes / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; D013745:Tetanus Toxoid; D015544:Inositol 1,4,5-Trisphosphate