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


CONCLUSIONS
Our data indicate that CD25+ regulatory T cells can be used for the treatment of systemic, antibody-mediated autoimmune diseases, such as CIA.
Leiden University Medical Center, Leiden, The Netherlands.
Mary E
ME
Morgan
Roelof
R
Flierman
Leonie M
LM
van Duivenvoorde
Hendrik J
HJ
Witteveen
Willem
W
van Ewijk
Jacob M
JM
van Laar
René R P
RR
de Vries
René E M
RE
Toes
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2