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Suppression of regulatory T cells by autoreactive CD8+ T effector cells in rheumatoid arthritis

ABSTRACT: Autoreactive CD8+ T effector (eff) cells specific to vimentin, actin cytoplasmic 1, or non-muscle myosin heavy chain 9 epitopes, evade regulatory T (Treg) cells in patients with rheumatoid arthritis undergoing worsening disease and who would become non-responders to tumor necrosis factor (TNF)-α inhibitor therapy, in contrast to autoreactive CD8+ T naïve (N) cells that are efficiently controlled by Treg cells in healthy individuals or patients who would become responders. Gene expression analysis revealed that the autoreactive CD8+ TN cell subset is comprised of a heterogeneous population of cells at various stages of development in healthy individuals or patients. Mechanistically, the production of TNF-α by CD8+ TN cells and the killing activity by CD8+ Teff cells in response to the relevant self-antigens influence the endorsement or suppression of Treg function, respectively. These data provide evidence of a previously undescribed role of such mechanisms in the progression and therapy of a prototypical human autoimmune disease, such as rheumatoid arthritis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE105162 | GEO | 2018/05/01

REPOSITORIES: GEO

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