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.