NOD mice manifest many features of autoimmune exocrinopathy (Sjögren's 
syndrome), a disease generally characterized by a chronic, progressive 
immunological attack against the exocrine tissues of the salivary and lacrimal 
glands. Previous studies using the NOD congenic partner strain, NOD.Igmu(null), 
defined an important role for B lymphocytes in the development of xerostomia, 
implicating autoantibodies reactive with the acetylcholine muscarinic receptor 
(M3R) as the possible effector mechanism. In the present study, we have examined 
the impact of the cytokine, interleukin (IL)-4, on autoimmune exocrinopathy by 
using the IL-4 gene knockout (KO) NOD mouse strain, NOD.IL-4-/-. Despite 
manifesting the physiological aberrations and marked leukocytic infiltration of 
the salivary glands characteristic of autoimmune xerostomia in NOD mice, the 
NOD.IL-4-/- mice do not develop xerostomia. However, NOD.IL-4-/- mice that 
received adoptively transferred T lymphocytes derived from NOD.Igmu-/- mice 
progress to xerostomia, thereby reversing the defect. While progression or lack 
of progression to xerostomia correlated with the ability of the NOD.IL-4-/- mice 
to express detectable anti-M3R autoantibodies, the precise mechanism of how IL-4 
influences the development of autoimmune xerostomia remains speculative.