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

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. Nanostring gene expression analysis was performed on RNA extracted from Naïve (N) and effector (Eff) CD8+ T lymphocytes, specific for apoptotic epitopes, sorted from patients with rheumatoid arthritis (P) and from healthy donors (HDs), and 26 samples were analysed: 5 N from HDs, 4 Eff from HDs, 9 N from P and 8 Eff from P.