title: The role of regulatory T cells in antigen-induced arthritis: aggravation of arthritis after depletion and amelioration after transfer of CD4+CD25+ T cells.
abstract: It is now generally accepted that CD4+CD25+ Treg cells play a major role in the prevention of autoimmunity and pathological immune responses. Their involvement in the pathogenesis of chronic arthritis is controversial, however, and so we examined their role in experimental antigen-induced arthritis in mice. Depletion of CD25-expressing cells in immunized animals before arthritis induction led to increased cellular and humoral immune responses to the inducing antigen (methylated bovine serum albumin; mBSA) and autoantigens, and to an exacerbation of arthritis, as indicated by clinical (knee joint swelling) and histological scores. Transfer of CD4+CD25+ cells into immunized mice at the time of induction of antigen-induced arthritis decreased the severity of disease but was not able to cure established arthritis. No significant changes in mBSA-specific immune responses were detected. In vivo migration studies showed a preferential accumulation of CD4+CD25+ cells in the inflamed joint as compared with CD4+CD25- cells. These data imply a significant role for CD4+CD25+ Treg cells in the control of chronic arthritis. However, transferred Treg cells appear to be unable to counteract established acute or chronic inflammation. This is of considerable importance for the timing of Treg cell transfer in potential therapeutic applications.
authors.affiliation: Institut fur Pathologie, Friedrich-Schiller-Universität, Jena, Germany. oliver.frey@med.uni-jena.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Frey
authors.forename: Peter K
authors.initials: PK
authors.lastname: Petrow
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Kerstin
authors.initials: K
authors.lastname: Siegmund
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
authors.forename: Alexander
authors.initials: A
authors.lastname: Scheffold
authors.forename: Alf
authors.initials: A
authors.lastname: Hamann
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000633:toxicity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine
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