Specific and long-lasting protection from collagen-induced arthritis and oil-induced arthritis in DA rats by administration of immunogens.

DA rats develop transient arthritis after subcutaneous immunization with adjuvant-oil, while chronic arthritis and collagen autoreactivity ensues when collagen is added to the oil. We show here that DA rats can be protected from oil-induced arthritis (OIA) and rat collagen-induced arthritis (rCIA) by addition of antigen to these arthritogenic inocula. We have investigated this remarkable phenomenon and demonstrate that both foreign and self antigens can be protective, apparently provided they are immunogenic; hence HSP-65kDa, ovalbumin, rat myelin basic protein, rat IgG and bovine albumin are effective while rat albumin is not. This protection is long-lasting and disease-specific because rats protected from rCIA resist a later attempt to induce arthritis, but not experimental autoimmune encephalomyelitis (EAE). Protection from rCIA depends neither on the blocking of humoral autoreactivity to collagen nor on a change in the isotype profile of anti-collagen antibodies. We demonstrate that immunogens can also be protective when injected intraperitoneally only a few days before onset of arthritis. Our results indicate that protection is mediated through bystander immune reactions towards the co-immunized antigen and that the arthritogenicity of a given provocation, be it adjuvants, microbes or autoantigens, may be a complex net result of arthritogenic and contra-arthritogenic immune reactions.

Restricted T cell receptor usage in DA rats during early collagen-induced arthritis.

We have investigated the usage of T cell receptor (TcR) V beta gene structures in DA rats undergoing homologous collagen-induced arthritis induced by immunization with homologous collagen type II emulsified in Freund's incomplete adjuvant. TcR V beta expression within freshly isolated inflamed synovial tissue (ST) and primary draining lymph nodes was analyzed in a semi-quantitative polymerase chain reaction assay. A highly restricted TcR V beta gene expression was observed in ST samples 2 days after onset of clinical disease, with V beta 6, 8.2 and 8.5 comprising more than 60% of the total V beta expression measured. The corresponding primary draining lymph nodes from the diseased animals showed some bias in V beta expression at this time but not as remarkable as that found in ST. One week after onset of disease, consistent V beta gene bias was much less evident in either site. These results indicate that T cells which infiltrate synovia early in disease are highly restricted with respect to V beta expression.

Percutaneous exposure of adjuvant oil causes arthritis in DA rats.

The arthritogenic properties of adjuvant oil upon percutaneous administration in DA rats was investigated. Groups of rats were administered single or repeated percutaneous applications of Freund's incomplete adjuvant (FIA) or olive oil on shaved skin with or without prior abrasion of the skin. Control rats were shaved and abrased only. A transient arthritis developed in 8/16 animals after repeated applications of FIA on abrased skin. The incidence of arthritis increased to 7/8 animals when FIA was repeatedly administered via filter paper on abrased skin and covered with a bandage. Histological examination of the arthritic joints showed proliferation of the synovial lining layer, infiltration of mononuclear cells and polymorphonuclear cells in the subsynovial tissue. Some bone and cartilage destruction was also seen. Repeated treatment with olive oil on abrased skin induced joint swelling in 3/15 animals, which did not, however, correspond to any microscopically observable signs of inflammation. Also, a single application of FIA on abrased skin or repeated applications of FIA without abrasion induced arthritis, although with low penetration, whereas control animals had no clinical signs of joint involvement. These findings demonstrate that percutaneous administration of adjuvant oil can cause arthritis in genetically susceptible animals.

Adjuvant oils induce arthritis in the DA rat. I. Characterization of the disease and evidence for an immunological involvement.

An intradermal injection of Freund's incomplete adjuvant oil (FIA) without further additives was shown to induce erosive polyarthritis in dark Agouti (DA) rats, but not in Lewis rats. Histological examination revealed joint inflammation, first with polymorphonuclear cells and synovial hyperplasia, and subsequently, with multinucleated giant cells. Both constituents of FIA, mineral oil and Arlacel A, as well as Pristane oil were arthritogenic, whereas vegetable oil were not. Re-administration of adjuvant oil after recovery failed to induce arthritis, thus making possible a role of specific immunity in this new form of arthritis in rats.