Antigen inhibition of collagen-induced arthritis is associated with up-regulation of IL-4 mRNA and induction of Ox40 on T cells in draining lymph nodes.
The addition of a foreign antigen to an inoculum completely inhibits the development of collagen-induced arthritis (CIA). However, the mechanism of this phenomenon, antigen -inhibition, is incompletely understood. Previous studies have demonstrated that the inhibition of arthritis is not mediated through suppression of the antibody response to cartilage antigens. In this paper we investigated cytokine mRNA levels in lymph nodes cells recovered 3, 7 or 16 days from animals immunized with either collagen II in IFA or OVA + collagen II in IFA. At day 7, but not at other time-points, IL-4 mRNA was up-regulated in the lymph nodes of OVA-inhibited non-arthritic animals compared to control animals which all developed arthritis. No significant differences between the two groups could be detected when expression of IFN-gamma, IL-2, TNF-alpha, IL-1beta or IL-10 mRNA was analysed. Flow cytometry analysis of draining lymph node cells demonstrated that the T cell marker Ox40 was up-regulated in the OVA-inhibited group. Our results indicate that the complete inhibition of CIA caused by addition of OVA to the collagen II inoculum is due to the presence of a TH2 environment resulting from an increased production of IL-4 mRNA and a parallel increase in Ox40+ T cells.
Mattsson
L
L
Division of Rheumatology, Centre for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Lundberg
K
K
Mussener
E
E
Jansson
A
A
Erlandsson Harris
H
H
Larsson
P
P
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D003094:Collagen; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005620:Freund's Adjuvant; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D018418:Th2 Cells / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D015854:Up-Regulation
D000941:Antigens; D016207:Cytokines; D012333:RNA, Messenger; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4; D010047:Ovalbumin; D003094:Collagen; D005620:Freund's Adjuvant