These probabilities differ markedly from that seen for the non-autoimmune B6

This analysis allows us to predict the potential for any antigen-reactive cell to reach any division stage and hence better appreciate the frequency of avoidance of tolerogenic mechanisms that require the coordinated progression of an activated CD4 T cell through at least four rounds of cell division. Intriguingly, the three autoimmune strains demonstrated indistinguishable probabilities of generating a daughter cell in any division peak; moreover, these probabilities differ markedly from that seen for the non-autoimmune B6 strain. In contrast, an activated CD4 T cell from the B6 strain has an almost 40% chance of achieving this advanced level of cell division. This finding indicates that an activated autoantigen reactive cell in the non-autoimmune background would be nearly four times more likely to achieve the advanced cell divisions where cytokine deviation and AICD are known to occur. Having demonstrated a profound diminishment in autoimmune strain CD4 T cell division at maximal concentrations of anti-CD3 Demethyleneberberine antibody, it was also important to assess the reactivity of these cells to other doses of this stimulus. This analysis is particularly important as the levels at which autoantigens are presented in vivo remain unknown. In Figure 2, dose-response curves for each autoimmune strain are presented and compared to the normal B6 curve. As the number of CD4 T lymphocytes present in splenocyte preparations from each strain is astragalin highly strain specific, we performed calculations based on normalized cell numbers following flow cytometric analysis. This analysis permitted examination of the activation properties inherent in whole splenocyte cultures, which were likely to be most reflective of the internal milieu of these animals. For each strain, the data is reported as a percent of maximal mitosis. It is also important to note that these maxima differ among the strains; the maximum proliferation achieved by CD4 lymphocytes on the B6 background is markedly greater than that achieved by the autoimmune strains.Even at the highest doses of antibody, the proliferation of the autoimmune strains is much less than that in prototypical nonautoimmune strains.