POS0402 CLONALLY EXPANDED CD38hi CYTOTOXIC CD8 T CELLS DEFINE THE T CELL INFILTRATE IN CHECKPOINT INHIBITOR-ASSOCIATED ARTHRITIS

  • Wang R
  • Singaraju A
  • Marks K
  • et al.
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Abstract

Immune checkpoint inhibitor (ICI) therapies that promote T cell activation have improved outcomes for advanced malignancies yet also elicit harmful autoimmune reactions. The T cell mechanisms mediating these iatrogenic autoimmune events remain unclear. Here we assayed T cells from joints of patients affected by ICI-induced inflammatory arthritis (ICI-arthritis), which can present clinically indistinguishable from rheumatoid arthritis (RA). Compared to the autoimmune arthritides RA and psoriatic arthritis (PsA), ICI-arthritis joints contained an expanded CD38hi CD127− CD8+ T cell subset that displays cytotoxic, effector, and interferon (IFN) response signatures. The abundance of CD38hi CD8 T cells in ICI-arthritis resulted from a limited number of clones that could be found proliferating in the joint. Exposure of synovial T cells to Type I IFN, more so than IFN-γ, induces the CD38hi cytotoxic phenotype. Relative to other CD8+ T cell subsets in the joints, the CD38hi population is distinct from a dysfunctional population and clonally most related to TCF7+ memory populations. Examination of synovial tissue from bilateral knee arthroplasty demonstrated considerable sharing of TCR clonotypes in the CD38hi CD8 T cell fraction from both knees. These results define a distinct CD8 T cell subset that may be directly activated by ICI therapy and mediate a tissue-specific autoimmune cellular reaction in patient joints.Competing Interest StatementThe authors have declared no competing interest.

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APA

Wang, R., Singaraju, A., Marks, K. E., Shakib, L., Dunlap, G., Cunningham-Bussel, A., … Rao, D. (2022). POS0402 CLONALLY EXPANDED CD38hi CYTOTOXIC CD8 T CELLS DEFINE THE T CELL INFILTRATE IN CHECKPOINT INHIBITOR-ASSOCIATED ARTHRITIS. Annals of the Rheumatic Diseases, 81(Suppl 1), 457.1-457. https://doi.org/10.1136/annrheumdis-2022-eular.3779

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