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 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.

• Publication year

  2010

• Venue

  Nature

• Publication date

  2010-09-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/nature09370PMID 20844537PMCID 3395240
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Disrupting the inhibitory interaction between CD8+ regulatory T cells and Qa-1+ follicular T helper cells leads to lethal systemic lupus erythematosus-like autoimmune disease.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review
• CD8+ regulatory T cells are an essential regulatory element for maintaining self tolerance and preventing murine autoimmune disease.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review

• cd8+ regulatory t cells

  cell type

  A CD8+ T-cell lineage with regulatory rather than effector function in the immune system.

  Aliases: CD8+ Treg, CD8 Treg

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review
• follicular t helper cells

  cell type

  A helper T-cell subset associated with follicular responses and germinal-center support.

  Aliases: Tfh cells, Tfh

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review
• murine autoimmune disease

  disease

  Autoimmune disease occurring in mice, used here as the disease context for the reported mechanism.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review
• qa-1

  molecule

  An MHC class Ib molecule expressed on the follicular T-helper cells discussed in the abstract.

  Aliases: Qa-1+

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review
• self tolerance

  immune state

  The immune state that limits responses against the body's own tissues and organs.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review
• systemic lupus erythematosus-like autoimmune disease

  disease

  A lupus-like autoimmune phenotype in mice characterized by systemic self-reactive immune pathology.

  Aliases: lupus-like autoimmune disease

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewmexicorea (qjvnbu8xg3) reviewAK (4715169a40) review

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