Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells

Arthritis Rheum. 2005 Jul;52(7):2212-21. doi: 10.1002/art.21195.

Abstract

Objective: Regulatory T cells play an important role in the prevention of autoimmunity and have been shown to be effective in the treatment of experimental colitis, a T cell-mediated and organ-specific disease. We previously demonstrated that intrinsic CD25+ regulatory T cells modulate the severity of collagen-induced arthritis (CIA), which, in contrast to colitis, is a systemic antibody-mediated disease and an accepted model of rheumatoid arthritis. We undertook this study to determine whether regulatory T cells have the potential to be used therapeutically in arthritis.

Methods: We transferred CD4+,CD25+ T cells into mice exhibiting arthritis symptoms, both immunocompetent mice and mice subjected to lethal irradiation and rescued with syngeneic bone marrow transplantation.

Results: A single transfer of regulatory T cells markedly slowed disease progression, which could not be attributed to losses of systemic type II collagen-specific T and B cell responses, since these remained unchanged after adoptive transfer. However, regulatory T cells could be found in the inflamed synovium soon after transfer, indicating that regulation may occur locally in the joint.

Conclusion: Our data indicate that CD25+ regulatory T cells can be used for the treatment of systemic, antibody-mediated autoimmune diseases, such as CIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / therapy*
  • Bone Marrow Transplantation
  • CD4 Antigens / biosynthesis
  • CD4 Antigens / immunology*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Forkhead Transcription Factors
  • Immunosuppression
  • Immunotherapy*
  • Mice
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation

Substances

  • CD4 Antigens
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • RNA, Messenger
  • Receptors, Interleukin-2