Cell-based immunotherapy with suppressor CB8+ T cells in rheumatoid arthritis

Eduardo Davila, Young Mo Kang, Yong Wook Park, Hirokazu Sawai, Xiaowen He, Sergey Pryshchep, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

The chronic persistence of rheumatoid synovitis, an inflammation driven by activated T cells, macrophages, and ibroblasts causing irreversible joint damage, suggests a failure in physiologic mechanisms that down-regulate and terminate chronic immune responses. In vitro CD8+CD28 -CD56+ T cells tolerize APCs, prevent the priming of naive CD4+ T cells, and suppress memory CD4+ T cell responses. Therefore, we generated CD8+CD28-CD56+ T cell clones from synovial tissues, expanded them in vitro, and adoptively transferred them into NOD-SCID mice engrafted with synovial tissues from patients with rheumatoid arthritis. Adoptively transferred CD8+CD28 -CD56+ T cells displayed strong anti-inflammatory activity. They inhibited production of IFN-γ, TNF-α, and chemokines in autologous and HLA class I-matched heterologous synevitis. Down-regulation of costimulatory ligands CD80 and CD86 on synovial fibroblasts was identified as one mechanism of immunosuppression. We propose that rheumatoid synovitis can be suppressed by cell-based immunotherapy with immunoregulatory CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)7292-7301
Number of pages10
JournalJournal of Immunology
Volume174
Issue number11
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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