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

Abstract

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.

Immunological Effects of d‐Penicillamine during Experimentally Induced Inflammation in Rats

“…Induction of adjuvant arthritis in Lewis rats by the injection of Mycobacterium butyricum in mineral oil led to an initial increase (on day 4) in the response of the lymph node cells to the T-cell mitogen Con A but not to the B-cell mitogen LPS, as measured by the incorporation of ^H-TdR into cellular DNA. T-cell activation by adjuvants has repeatedly been described [1,27], and peripheral blood lymphocytes with increased responsiveness to Con A have been found in rats with adjuvant arthritis shortly after the induction of the disease [23]. In the present experiments this initial increase in T-cell responsiveness was followed by inhibition of H-TdR incorporation in both Con-A-and LPS-stimulated lymph node cells, 14 days after the induction of the disease.…”

“…Studies with gradient-separated cells showed that the response to Con A of the cell fraction containing T-helper activity (light-density cells [28]) was decreased on day 7 in cultures from untreated and D-penicillamine-treated adjuvant arthritic rats. This decrease was not dependent on the presence of macrophages and may be due to the release of Con-A-responsive lymphocytes into the bloodstream after administration of adjuvant [23]. On day 14 suppressive macrophages were found in cultures of light-density cells from untreated adjuvant arthritic rats but not in the corresponding cultures from Dpenicillamine-treated rats.…”

The inflammatory response to lymph node cells from adjuvant‐diseased rats. Relative contributions of donor and recipient cell populations

“…1979). Lymph node cells from FCA-treated Wistar rats, which are relatively insensitive to the development of arthritis (Kahan et al, 1976), only stimulated granuloma formation when transferred in large numbers into small sponge implants (Parnham et aZ.). In more recent studies, (Parnham 1980), we found that lymph node cells transferred from Wistar donor rats failed to stimulate granuloma formation when injected into the large sponges used in the present study, even when 108 cells per sponge were transferred.…”

Susceptibility of Two Colonies of Wistar Rats to Inflammation, with Particular Reference to Delayed Hypersensitivity

“…There is accumulating evidence for a genetical link to the susceptibility to adjuvant-induced arthritis [Swingle et al, 1969;Rosenthal, 1970;Currey, 1970;Kahan et al, 1976] and EAE [Paterson and Harwin, 1963;Levine and Wenk, 1961;Hughes and Stedronska, 1973] in rats.…”