Cytokine Production by Activated T Cells in Common Variable Immunodeficiency

Background: Common variable immunodeficiency (CVID) is the most common symptomatic antibody deficiency. It is characterized by hypogammaglobulinemia, increased susceptibility to recurrent infections, autoimmunity, and malignancies. Objectives: To determine whether patients with CVID have cytokine production defects after T-cell activation and to assess whether or not these are correlated with markers of severe disease. Methods: Twenty-seven patients with CVID and 17 healthy volunteers were investigated. Peripheral blood mononuclear cells were cultured under standard conditions in the presence and absence of phytohemagglutinin. Subsequent cell proliferation and cytokine release were measured and compared between stimulated and unstimulated cells. Results: A general enhancement in cytokine production was observed in both CVID patients and controls after stimulation. However, we detected a lower production of interferon-gamma in CVID patients than in controls (P=.026). A production defect for at least 1 cytokine was observed in 12 patients. Ten of these failed to generate protective titers in response to the polysaccharide vaccine, and the frequency of bronchiectasis in this group of patients was 91.7%. Cytokine release correlated strongly with cell proliferation. Conclusions: This study indicates that some CVID patients have T-cell proliferation and secretory defects and that these may be associated with severe manifestations of disease. Screening for such defects could permit more effective monitoring and therapeutic strategies for CVID patients.