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Autoimmunity

Benefits of exhaustion

Nature Reviews Immunology volume 15, page 468 (2015)Cite this article

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a signature of exhaustion in CD8+ T cells correlated with a low risk of relapse

In order to investigate the mechanisms driving relapsing autoimmunity, the authors analysed the transcriptome of purified CD4+ and CD8+ T cells isolated from 44 patients with active, untreated anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) disease or from 23 patients with active, untreated systemic lupus erythematosus (SLE). Using several different analysis methods, they found that a gene expression signature in CD4+ T cells that is associated with co-stimulation correlated with disease relapse, whereas a signature of exhaustion in CD8+ T cells correlated with a low risk of relapse and thus, a better prognosis. This suggests that a transcriptional signature of CD8+ T cell exhaustion, in conjunction with a signature of low CD4+ T cell co-stimulation, may be associated with a favourable long-term outcome in autoimmune diseases. Indeed, CD8+ T cells from patients with a good disease prognosis were characterized by the expression of a distinct subset of exhaustion-associated co-inhibitory receptors. Furthermore, a subgroup of patients with both early and recurrent relapses could be identified from independent cohorts of patients with SLE, AAV or inflammatory bowel disease based on the absence of a CD8+ T cell exhaustion signature.

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References

  1. McKinney, E. F. et al. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature http://dx.doi.org/10.1038/nature14468 (2015)

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  1. Olive Leavy
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Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. (in the press)

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Leavy, O. Benefits of exhaustion. Nat Rev Immunol 15, 468 (2015). https://doi.org/10.1038/nri3890

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