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

Article

关键词: SYSTEMIC-LUPUS-ERYTHEMATOSUS;    AUTOIMMUNE-DISEASE;    B-CELLS;    SUPPRESSION;    T-HELPER-2;    GENERATION;    EXPANSION;    IL-15;    IL-21;    MICE;   

DOI  :  10.1038/nature09370

来源: SCIE

【 摘 要 】

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(1). Regulatory T cells (T-reg) 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(2). 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.

【 授权许可】

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