Vitamin A is necessary for acquisition, but not for expression or progression, of CNS autoimmunity.

Vitamin A (VitA) and its derivative retinoic acid (RA) are essential for immunological responses. In VitA deficient (VAD) mice, acquisition of effector responses is impeded, but little is known about maintenance and expression of previously acquired effector function under the VAD conditions. We examined the impact of VAD on progression of autoimmune diseases using two models of uveitis, experimental autoimmune uveitis (EAU) induced by active immunization and spontaneous uveitis in retina-specific T cell receptor transgenic (R161H) mice, and in the model of experimental autoimmune encephalomyelitis (EAE). VAD was induced by dietary lack of VitA from before birth, or by daily injections of a pan-RA receptor inhibitor BMS493 in adult mice fed with the standard diet. VAD mice were essentially resistant to induction of EAU or EAE and displayed impaired effector T cell responses. Defective priming/acquisition of effector function by VAD T cells was also evident. By contrast, spontaneously uveitic R161H mice fed with VAD diet, in which priming of pathogenic T cells occurs before onset of full VAD, only moderately attenuated uveitis compared to VitA sufficient R161H mice. To reconcile somewhat different results between induced model and spontaneous model of uveitis, we examined EAU in partial VAD mice or adoptive transfer into VAD hosts. The results supported that effector T cells primed in VitA-sufficient environment were able to function in VAD environment and induced EAU. We conclude that although priming of naïve T cells in the VAD environment is defective, effector function acquired under VitA sufficient conditions is maintained and can be expressed under VAD conditions. Because dietary lack of VitA is rarely profound and may be seasonal, our findings may shed light on immunity and autoimmunity in geographical regions where dietary VitA is limiting.