title: Reduced IL-2 expression upon antigen stimulation is accompanied by deficient IL-9 gene expression in T cells of patients with CVID.
abstract: Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestation of the disease as well as in the underlying mechanisms leading to the immunodeficiency. In a previous study we identified a subgroup of patients with a primary immunodeficiency disease affecting IL-2 and IFN-gamma gene expression. The T cells of these patients revealed impaired proliferative response and reduced levels of IL-2 and IFN-gamma-specific mRNA after antigen stimulation in vitro, while cellular and molecular response to phorbol ester and the calcium ionophore ionomycin (PMA+IM) or anti-CD3 monoclonal antibodies (MoAbs) (OKT3) were comparable to those of healthy control individuals. Here we show that stimulation of these patients' T cells with tetanus toxoid (TT) resulted in dramatically reduced levels of IL-2, IL-9 and IFN-gamma mRNA, while IL-3 gene expression in three patients was comparable or even increased to the healthy controls. As expected, addition of exogenous IL-2 to tetanus toxoid pulsed cultures had virtually no effect on IL-2 transcription, but corrected the defect in IL-9 gene expression, while IFN-gamma mRNA levels were still reduced. In conclusion, these data suggest that recombinant IL-2 alone is not able to induce the IL-9 gene adequately in our patients, but clearly increases IL-9 mRNA levels in combination with tetanus toxoid.
authors.affiliation: Institute of Immunology, University of Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Hauber
authors.forename: M B
authors.initials: MB
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Maris
authors.forename: M M
authors.initials: MM
authors.lastname: Eibl
mesh_terms: D000941:Antigens / Q000276:immunology; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D007377:Interleukin-3 / Q000096:biosynthesis; D016906:Interleukin-9 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D007376:Interleukin-2; D007377:Interleukin-3; D016906:Interleukin-9; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma