T cell memory differentiation in early autoimmune disease

Chronic T cell activation and memory differentiation contribute essentially to the perpetuation of ongoing autoimmune processes by diverse mechanisms. Apart from this, chronically activated memory T cells can shut down synthesis of IL-2 which promotes regulatory T cell (Treg) defects and which in turn facilitates tolerance breakdown. However, little is known about the factors which drive memory formation and chronicity in an early stage of autoimmune disease when clinical symptoms are still unapparent. In the (NZBxNZW) F1 mouse model of lupus, signs of increased T cell activation and memory differentiation are detectable in lymphoid tissues long before the development of organ manifestations and even before the generation of autoantibodies, proposing that aberrant T cell activation is an early event in autoimmunity. In addition, Treg from these mice are in a highly activated state suggesting that active counter-regulation is already taking place at this early stage of disease.