ANHYDRORETINOL - A NATURALLY-OCCURRING INHIBITOR OF LYMPHOCYTE PHYSIOLOGY

Vitamin A (retinol) is an essential cofactor for growth of B lymphocyt es in culture and for activation of T lymphocytes by antigen receptor- mediated signals. 14-hydroxy-4,14-retro-retinol (14-HRR) a metabolite of retinol, has been implicated as the intracellular mediator of this effect. Anhydroretinol (AR) is a retinol derivative with retro structu re produced in activated human B lymphocytes and the insect cell lines SF 21 and Schneider S2. AR reversibly inhibits retinol- and 14-HRR-de pendent effects and blocks B lymphocyte proliferation as well as activ ation of resting T lymphocytes. The intracellular signaling pathway bl ocked by AR in T cell activation is distinct from the calcineurin/inte rleukin 2 pathway inhibitable by cyclosporine A or FK-506.