Absence of  “Original Antigenic Sin” in Autoimmunity Provides an Unforeseen Platform for Immune Therapy

In this issue of The Journal of Experimental Medicine, Tuohy et al. study the spreading of the autoimmune response to myelin antigens in experimental autoimmune encephalomyelitis (EAE) and its likely human counterpart, multiple sclerosis (MS) (1). They demonstrate that as disease develops in EAE and MS, reactivity to the initiating antigen diminishes, and an orderly and definable set of new immune reactivities arises. The data are clear and the scope of the study in humans and in experimental animals is broad. For example, the investigators elegantly look at T cells in the central nervous system (CNS) in EAE to see whether the reduction in peripheral activity is due to sequestration of such T cells in the brain and spinal cord. The answer to this question is a resounding “no.” Loss of reactivity is not due to sequestration of the immune response in the CNS. The implications...