Here, we recorded several features of anergy, an acquired state of T cell functional hyporesponsiveness (53), in MOG-specific T cells exposed to OM-MOG in vitro and in vivo; loss of the ability to produce and respond to the autocrine growth factor IL-2; reduced proliferation in response to MOG; high production of FR4 by CD4+FoxP3-CD44+ cells in the spleen of therapeutic OM-MOG B6 mice. The gene discussed is CD4; the disease is ocular melanoma.