Adjuvant arthritis (AA) was initially observed by accident when complete Freund's adjuvant (CFA) was used for immunization (Pearson, 1956). Since then, induced AA has been used extensively as a model for rheumatoid arthritis, although some histopathological differences exist. By its nature, where the disease is induced by a bacteria-containing substance, AA can also serve as a model for reactive arthritis. Some of the additional clinical features of reactive arthritis are also seen in AA: e.g., iridocyclitis, nodular skin lesions, genitourinary lesions, and diarrhea. Besides this, the model features some aspects of rheumatic fever: e.g., ulcerative colitis and sarcoidosis (Pearson et al., 1961).
Compared to other models of induced experimental autoimmunity, AA is relatively unique in that disease is induced by substances that do not contain a defined self antigen. In fact, no joint-associated target antigen has been defined with certainty so far, although proteo-glycans are likely candidates (van Eden et al., 1985; van Vollenhoven et al., 1988). For this reason, AA can be used for studying basic mechanisms of how external triggering may lead to undesired self recognition. A possible human analog of AA is the transient arthritis seen in cancer patients treated by immuno-therapy with Mycobacterium bovis strain BCG (Torisu et al., 1978).
AA is T cell mediated. Disease can be transferred by ConA-expanded polyclonal T cells (Taurog et al., 1983) or by mycobacteria-spe-
cific T cell lines or clones in immunosup-pressed recipients (Holoshitz et al., 1983). Primed T cells suitable for transfer can be collected from inguinal lymph nodes around day 14 after immunization for rats injected at the base of the tail, or from popliteal lymph nodes at day 9 after immunization for rats injected in the footpads. Passive disease following adoptive transfer (5 x 106 to 5 x 107 T cells) resembles active disease to a great extent, although the severity and duration may be reduced (Stanescu et al., 1987). A T cell clone (A2b) that transferred AA was found to respond to mycobacteria and also to cartilage proteo-glycans, a case of molecular mimicry (van Eden et al., 1985). Subsequently, clone A2b was found to have specificity for a 65-kDa myco-bacterial heat-shock protein, a member of the hsp60 family (van Eden et al., 1988).
The classical method of inducing AA is with mycobacteria in incomplete Freund's adjuvant. Alternatively, arthritis can be induced in some strains of rats using incomplete Freund's or other oily substances in the absence of added mycobacteria. This can be seen with mineral oil (Kleinau et al., 1991) or with Avridine (also known as CP20961), which is a synthetic non-antigenic lipoidal amine (Billingham et al., 1990; Anderton et al., 1995). In some rat strains, Avridine-induced arthritis may develop into a rather chronic form of arthritis (Vingsbo et al., 1985).
Lewis rats are frequently used for induction of AA. Although relative sex preferences have been reported in susceptible rats, there are no
Animal Models for Autoimmune and
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