Ly49 C/I-dependent NKT cell-derived IL-10 is required for corneal graft survival and peripheral tolerance.

Similar to their activity on NK cells, Ly49 molecules play a pivotal role in influencing how NKT cells respond. It is known that Ly49 C/I is an inhibitory receptor capable of down-modulating proliferation, IFN-gamma response, and cytotoxic activity in cells that express it. In a model of peripheral tolerance induced via the eye, we observed that Ly49 C/I-positive, invariant NKT cells were required. To test if the NK inhibitory receptor functionally contributed to tolerance development, we used blocking antibody, in vivo and in vitro, to interfere with the development of antigen-specific suppression. A result of blocking ligation of Ly49 C/I inhibitory receptor prevented NKT cell production of IL-10 and the subsequent development of tolerance. Ly49 C/I-blocking antibodies also prevented corneal graft survival, a phenomenon dependent on eye-induced tolerance. Furthermore, in the presence of TCR stimulation, cross-linking of Ly49 C/I on CD4(+) NKT cells stimulated an increase in IL-10 mRNA and a decrease in IFN-gamma. The concept of Ly49 inhibitory receptors regulating immune reactivity to self by regulating immune activity of individual cells is thus expanded to include a role for the inhibitory receptors in the more global process of peripheral tolerance to foreign antigens.

Vitamin E deficiency in dogs with retinal pigment epithelial dystrophy.

The role of vitamin E deficiency in the development of retinal pigment epithelial dystrophy was investigated in 11 cocker spaniels and four other dogs. The concentration of alpha-tocopherol was measured by high performance liquid chromatography in plasma samples obtained from the affected dogs and from 28 ophthalmoscopically normal, healthy control dogs. The mean (sd) plasma alpha-tocopherol concentration in the normal dogs was 20.2 (7.1) microg/ml, compared with 1.14 (0.67) microg/ml in the 11 affected cocker spaniels. The difference between the two groups remained highly significant when the alpha-tocopherol concentrations were expressed relative to the concentrations of the plasma lipids cholesterol and triglycerides. Low plasma concentrations of alpha-tocopherol were observed in the four affected dogs of other breeds, but the finding was not so consistent. The plasma lipid concentrations were normal in the affected dogs. The deficiency of alpha-tocopherol in the affected dogs appeared to be primary, because there was no clinical, biochemical or pathological evidence of underlying disease, or any indication of a dietary deficiency which might have contributed to the low concentrations of alpha-tocopherol.

Clinical and pathological observations in English cocker spaniels with primary metabolic vitamin E deficiency and retinal pigment epithelial dystrophy.

Fifteen English cocker spaniels with confirmed vitamin E deficiency were examined physically, ophthalmologically and neurologically. Eleven of them had clinical signs of neurological dysfunction which included ataxia, proprioceptive deficits, abnormal spinal reflexes and muscle weakness. In the two dogs examined histopathologically there was central neuronal fibre degeneration with prominent neuroaxonal dystrophy, particularly within the sensory relay nuclei of the brainstem, and one of the dogs had severe intestinal lipofuscinosis.