IL-4-dependent effector phase in autoimmune exocrinopathy as defined by the NOD.IL-4-gene knockout mouse model of Sjogren's syndrome

NOD mice manifest many features of autoimmune exocrinopathy (Sjogren's synd rome), a disease generally characterized by a chronic, progressive immunolo gical attack against the exocrine tissues of the salivary and lacrimal glan ds. Previous studies using the NOD congenic partner strain, NOD.Ig mu (null ), defined an important role for B lymphocytes in the development of xerost omia, implicating autoantibodies reactive with the acetylcholine muscarinic receptor (M3R) as the possible effector mechanism. In the present study, w e have examined the impact of the cytokine, interleukin (IL)-4, on autoimmu ne exocrinopathy by using the IL-4 gene knockout (KO) NOD mouse strain, NOD .IL-4(-/-). Despite manifesting the physiological aberrations and marked le ukocytic infiltration of the salivary glands characteristic of autoimmune x erostomia in NOD mice, the NOD.IL-4(-/-) mice do not develop xerostomia. Ho wever, NOD.IL-4(-/-) mice that received adoptively transferred T lymphocyte s derived from NOD.Ig mu (-/-) mice progress to xerostomia, thereby reversi ng the defect. While progression or lack of progression to xerostomia corre lated with the ability of the NOD.IL-4(-/-) mice to express detectable anti -M3R autoantibodies, the precise mechanism of how IL-4 influences the devel opment of autoimmune xerostomia remains speculative.