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

Abstract

SUMMARYThe addition of a foreign antigen to an inoculum completely inhibits the development of collageninduced 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-g , IL-2, TNF-a , IL-1 b 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 OVAinhibited 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.

Role of soluble Fas ligand in autoimmune diseases

“…If Th1 cells are deleted from joints, the evolvement of joints in CIA may be lighter. Mattsson et al [20] reported that the T cell marker O×40 was up-regulated in OVA-inhibited nonarthritic animals compared to control CIA animals. They found that the complete inhibition of CIA caused by addition of OVA to the collagen II inoculum was due to the presence of a TH2 environment resulting from an increased production of IL-4 mRNA and a parallel increase in O×40+ T cells [20] .…”

“…Collagen induced arthritis (CIA) has become a commonl animal model in studing the pathogenesis of rheumatoid arthritis [2,17] . Many potential factors involved in CIA [2,[18][19][20] , Th1 cells are mainly involved in the CIA. If Th1 cells are deleted from joints, the evolvement of joints in CIA may be lighter.…”

Arthritogenicity of collagen type II is increased by chlorination

“…The Taqman TM method was used for quantitative polymerase chain reaction (PCR) analysis of cDNA (Perkin Elmer, Norwalk, CT, USA) according to the manufacturer’s instructions. Primers and probes for IL‐1β and IFN‐γ were designed using the software PrimerExpress TM (Perkin Elmer) [19].…”

A pH-induced modification of CII increases its arthritogenic properties

“…The TaqManÔ methodology was used for quantitative PCR analysis of cDNA (Perkin Elmer, Norwalk, CT, USA) according to the manufacturers' instructions. Primers and probes were designed using the software PrimerExpressÔ (Perkin Elmer) [27].…”