Cell-based immunotherapy with suppressor CD8+ T cells in rheumatoid arthritis.

Abstract

The chronic persistence of rheumatoid synovitis, an inflammation driven by activated T cells, macrophages, and fibroblasts 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-gamma, TNF-alpha, and chemokines in autologous and HLA class I-matched heterologous synovitis. 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.

• Authors: Eduardo Davila, Young Mo Kang, Yong Wook Park, Hirokazu Sawai, Xiaowen He, Sergey Pryshchep, Jörg J Goronzy, Cornelia M Weyand
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 11 Pg. 7292-301 (Jun 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15905576 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• B7-2 Antigen
• CD28 Antigens
• CD56 Antigen
• CD86 protein, human
• Cd86 protein, mouse
• HLA-A2 Antigen
• Membrane Glycoproteins

Topics

• Adoptive Transfer (methods)
• Animals
• Antigen Presentation (immunology)
• Antigen-Presenting Cells (immunology, metabolism)
• Antigens, CD (biosynthesis)
• Arthritis, Rheumatoid (immunology, pathology, therapy)
• B7-2 Antigen
• CD28 Antigens (biosynthesis, metabolism)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD56 Antigen (biosynthesis)
• Cell Communication (immunology)
• Cell Line
• Cell Line, Tumor
• Clone Cells
• Down-Regulation (immunology)
• Fibroblasts (immunology, metabolism, pathology)
• HLA-A2 Antigen (immunology)
• Humans
• Immunophenotyping
• Lymphocyte Activation (immunology)
• Membrane Glycoproteins (antagonists & inhibitors, biosynthesis)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Synovial Membrane (immunology, metabolism, pathology)
• T-Lymphocytes, Regulatory (immunology, metabolism, transplantation)