The aim of this project is to determine the role of abnormal lymphokine/cytokine expression in the immunopathogenesis of common variable immunodeficiency (CVI). During the present period we have identified significant abnormalities in the expression of certain lymphokine genes in a group of patients with CVI. We examined T cell function in CVI by measuring the expression lymphokine genes in mitogen-activated T cells. The results show that T cells from patients with CVI exhibit deficient production of IL-2, IFN-gamma, IL-4, and IL-5. These defects are selective since T cells from patients with CVI retain a normal capacity to express IL-2Ralpha, c-myc and to proliferate. Further studies indicate that the deficient production of IFN-gamma by patient T cells is partially due to the abnormality of IL-2 production as the levels of IFN-gamma mRNA detected during the initial, IL-2 independent phase of T cell activation were normal and in vitro treatment with recombinant IL-2 was able to normalize IFN-gamma production by PHA-stimulated patient cells. Finally, supernatants from PHA-activated cultures of patients PBMCs were deficient in their ability to support Ig secretion by SAC-activated normal B cells suggesting that these T cell abnormalities may contribute to the pathogenesis of this syndrome. These results point to a profound abnormality of T cell function in patients with CVI that may play an important role in the pathogenesis of this syndrome.