Experimental autoimmune arthritis in mice. II. Early events in the elicitation of the autoimmune phenomenon induced by homologous type II collagen.

Intradermal injection of 100 micrograms of native homologous type II collagen (CII) into DBA/1-susceptible mice induced a progressive and chronic polyarthritis. This experimental autoimmune arthritis (EAA) closely mimicked the clinical evolution of human rheumatoid arthritis (RA) except for the sex linkage. Males were highly susceptible to EAA induction even when the amount of autoantigen injected was reduced to 25 micrograms. Conversely, females remained resistant to the disease even when a booster injection of 50 micrograms was administered. With regard to age, no major difference in the incidence was observed, although younger males developed a more severe arthritis than older ones. Anti-CII autoantibodies were detected in all immunized animals, regardless of the presence or absence of joint pathology. However, in arthritic mice, the onset of the disease was associated with a predominance of IgG2a autoantibodies. Kinetic studies revealed that females as well as males exhibited early histological lesions and detectable humoral responses toward mouse CII as of the second week postimmunization. Moreover, a specific cellular autoreactivity to homologous CII occurred in different lymphoid organs with a higher intensity in females than in males. Taken together, these findings suggest that homologous CII injection induces an early subclinical arthritis that develops progressively in all immunized mice, but would be down-regulated several weeks after priming, exclusively in females.