Adjuvant polyarthritis. vii. The role of type ii collagen in pathogenesis

Abstract

The development of immune response in rats directed toward EL4 cells, after the injection of EL4 cells suspended in a saline/oil emulsion, was enhanced by the incorporation of Mycobacterium into the saline/oil emulsion; the incorporation of type I1 collagen into the salineacetic acid/oil emulsion in concentrations ranging from 0.5-25 pg/ml had no apparent effect on the development of immune response. The incorporation of type I1 collagen into the saline-acetic acidloil emulsion at higher concentrations (100 pg and 1.0 mg/ml) significantly suppressed both the humoral and the cell-mediated immune response. Pretreatment of rats with the maximal subarthritogenic dose of complete Freund's adjuvant prevented the development of arthritis in response to a subsequent injection of an arthritogenic dose of the same adjuvant, but had no effect on the development of type I1 collagen-induced arthritis. These observations suggest that adjuvant arthritis and the type I1 collagen-induced arthritis are distinctly different diseases.Adjuvant arthritis in the rat is believed to arise from an aberrant immune response to antigen(s) whose identity remains elusive. The disease may be the result of a delayed hypersensitivity response to bacilli or The endogenous sensitizing immunogen responsible for the development of adjuvant arthritis has been suggested by Trentham and coworkers ( 3 ) to be type I1 collagen. This conclusion was based on their observations that chronic arthritis in the rat, similar to the classic adjuvant arthritis, can be induced by an oily preparation of type I1 collagen (43) and that rats with classic adjuvant arthritis exhibited cellular and humora1 immunity to homologous type I1 collagen (3). Conversely, Cremer et a1 (6) suggested that collageninduced arthritis is an entity distinct from adjuvant arthritis, dependent upon the unique immunogenicity of type I1 collagen in the rat. Our objective in this investigation was to ascertain whether an autoimmune response to type I1 collagen underlies the pathogenesis of both type I1 collagen-induced and adjuvant-induced polyarthritis in the rat. MATERIALS AND METHODSAnimals. Outbred male Sprague-Dawley rats, 4-8 weeks of age, weighing from 120-250 gm, were purchased from Simonsen Laboratory, Gilroy, CA. These rats were housed in metal cages and given water and standard rat chew ad libitum.

Synergy between adjuvant arthritis and collagen-induced arthritis in rats.

“…The conclusion that AA and CIA have different pathogenetic mechanisms is consistent with the findings of several investigators, who have reported that significant levels ofanti-CII do not develop in AA rats (25)(26)(27), that arthritogenic cloned antimycobacterial T cells do not react with type II collagen (13), and that AA and CIA are not susceptible to cross-tolerization (21,25,26). While there have also been reports of suppression of AA by administration of CII (27,28), these reports are not necessarily in conflict with our findings or conclusions, since the mechanism of this suppression may not be antigen-specific.…”

Testicular‐Associated Immune Deviation and Prevention of Adjuvant‐Induced Arthritis by Three Tolerization Methods

“…Antibodies to type II collagen, although of controversial significance in the pathogenesis of RA [42], are present in a significant proportion of patients [41], but the cellular immune response to collagen would be more relevant, and knowledge about that is scanty. In the animal model of AIA there is definitely a cellular response to collagen [43,44], and it has been used in AIA prevention [45]. A number of other candidate autoantigens for RA are available [46], and recently hopes have been raised that new important inciting antigens have been found [see reference 47 and also G. S. Panayi, Invited talk at the 1998 ACR San Diego national meeting].…”

Adjuvant polyarthritis. VIII. Differences in immunopathogenesis between type II collagen arthritis and adjuvant arthritis

“…The inbred Lewis strain, which is one of the most susceptible to adjuvant arthritis, is much less susceptible for developing collagen arthritis than the outbred SpragueDawley or the Wistar strain 1191. (4) The ability of Freund's type adjuvants to induce arthritis in rats appears to depend, at least partly, on the immuno-enhancing activity of the preparations [8], whereas, oily preparations of type II collagen has no adjuvant activity [ 11,12] and their ability to induce arthritis depends upon the unique immunogenicity of type II collagen [ 11,171. (5) Adjuvant arthritis seems to be primarily a disease of delayed hypersensitivity.…”

“…Trentham induced by an oily preparation of type II collagen [9, 10], and (2) rats with classic adjuvant arthritis exhibited cellular and humoral immunity to homologous type II collagen [7]. This view has not been supported by more recent studies [11,12], which suggested that adjuvant arthritis and type II collagen arthritis are distinctly different diseases. The present investigation was conducted in an attempt to resolve the controversy.…”