Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance

HJ Kim, B Verbinnen, X Tang, L Lu, H Cantor - Nature, 2010 - nature.com
HJ Kim, B Verbinnen, X Tang, L Lu, H Cantor
Nature, 2010nature.com
The ability to produce vigorous immune responses that spare self tissues and organs
depends on the elimination of autoreactive T and B cells. However, purging of immature and
mature self-reactive T and B cells is incomplete and may also require the involvement of
cells programmed to suppress immune responses. Regulatory T cells (Treg) belonging to
the CD4+ T-cell subset may have a role in preventing untoward inflammatory responses, but
T-cell subsets programmed to inhibit the development of autoantibody formation and …
Abstract
The ability to produce vigorous immune responses that spare self tissues and organs depends on the elimination of autoreactive T and B cells. However, purging of immature and mature self-reactive T and B cells is incomplete and may also require the involvement of cells programmed to suppress immune responses. Regulatory T cells (Treg) belonging to the CD4+ T-cell subset may have a role in preventing untoward inflammatory responses, but T-cell subsets programmed to inhibit the development of autoantibody formation and systemic-lupus-erythematosus-like disease have not yet been defined. Here we delineate a CD8+ regulatory T-cell lineage that is essential for the maintenance of self tolerance and prevention of murine autoimmune disease. Genetic disruption of the inhibitory interaction between these CD8+ T cells and their target Qa-1+ follicular T-helper cells results in the development of a lethal systemic-lupus-erythematosus-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.
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