Inhibition of follicular T helper cells by CD8(+) Treg is essential for self tolerance

The ability to produce vigorous immune responses that spare self tissues and organs depends on elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may require additional censorship by cells programmed to suppress immune responses (1). Regulatory T cells belonging to the CD4(+) T cell subset may play a role in preventing untoward inflammatory responses, but T cell subsets programmed to inhibit the development of autoantibody formation and SLE-like disease have not been defined (2). Here we delineate a CD8(+) regulatory T cell lineage that is essential for maintenance of self tolerance and prevention of autoimmune disease. Genetic disruption of the inhibitory interaction between these CD44(+) ICOSL(+) CD8(+) T cells and their target Qa-1(+) follicular T helper cells results in the development of a lethal SLE-like autoimmune disease. These findings define a sublineage of CD8 T cells programmed to suppress rather than activate immunity that represents an essential regulatory element of the immune response and a guarantor of self tolerance.