Adjuvant-induced arthritis in four inbred strains of rats. An in vitro study of peripheral T and B lymphocytes.

The lymphoblastic response (LTT) to non-specific mitogens (PHA, PWM and ConA) of peripheral lymphocytes was investigated at days 0, 7, 14, 21 and 28 after adjuvant injection in four strains of inbred rats: Wistar (WAG), Long Evans (LE), Lewis (LEW) and Brown Norway (BN). LTT was assessed by using 18 hours H3 TdR incorporation in 5 days cultures of whole blood (micromethod). The statistical treatment of data, using principal components multifactorial analysis and analysis of variance showed a striking difference between strains. In control animals the responses to PHA and PWM were correlated and were higher in LE and WAG than in LEW and BN (BN=LEW less than LE=WAG). The response to ConA was independent of that to the other mitogens. It was generally low, but significantly higher in LEW and BN than in WAG and LE. In adjuvant-injected animals the responses to PHA and PWM were still correlated, but modified compared to control: in LE and LEW, but not in WAG and BN, a marked decrease of the response was found, reaching a minimum value within days 7 and 14. In the same time the response to ConA increased in the four strains, later in LE than in the others. However the intensity of the ConA response varied from one strain to another: it was constantly low in LE and WAG compared to LEW and BN. So the most striking modification of LTT were observed in LE and LEW, which both developed the most severe arthritis. However these different behaviours after adjuvant injection were not explained by the initial level of LTT to the different mitogens. These data suggest that the development of intense arthritis is associated with the proliferation and the release into the blood stream of a lymphocyte subpopulation, which exhibits a low response to PHA and PWM and a high response to ConA. These LTT modifications are not paralleled by quantitative variations of B-cells assessed by surface Ig immunofluorescent staining and EAC rosetting.