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 variabie 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 β-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.