Loss of CD154 impairs the Th2 extrafollicular plasma cell response but not early T cell proliferation and interleukin-4 induction

Ligation of CD40 by CD4 T cells through CD154 is key both to germinal centre induction and follicular T-dependent Ig class switching, but its requirement for aspects of T cell priming and extrafollicular antibody responses is less clear. Here comparison of the T helper (Th) type 2 response in lymph nodes from wild-type mice and CD154-deficient mice after immunization with alum-precipitated antigen reveals selective effects of this immunodeficiency. The timing and magnitude of the early interleukin (IL)-4 induction and proliferation in T cells of the T zone were unaltered by CD154 deficiency. As expected, germinal centres were not induced. Additionally the T-dependent extrafollicular antibody response, which initially requires T cell help but expands without further T cell involvement, was severely curtailed. The median number of extrafollicular antigen-specific plasma cells was 370-fold lower in CD154-deficient mice. Of these plasma cells the median proportion that had switched to IgG1 was <5%, while in wild-type mice the proportion was 89%. Surprisingly, some CD154-deficient lymph nodes showed substantial switching to IgG1. Commensurately, increases in γ1 germline transcripts and Blimp-1 mRNA were observed, albeit significantly lower than in controls, but activation-induced cytidine deaminase mRNA was undetectable in CD154-deficient mice. These experiments demonstrate that the acquisition of some T cell priming characteristics can be CD154-independent; in contrast, T-dependent extrafollicular responses require CD154. Thus functional CD154 ligation during the first encounter of T cells and B cells in the T zone is critical for follicular and extrafollicular antibody responses

Collaborative Decision-Making in Non-formal Planning Settings

Planning initiatives outside the formal planning system can constitute a favourable environment for implementing and analysing collaborative decision-making processes. The conceptualisation of the decision-making context in the light of the Policy Network analysis helps to better understand the underlining conditions, as well as their influence in the outcomes. In the case under analysis, were the decision-making conditions were of co-responsibility and power-sharing, the challenge has been to warrant the effectiveness of the decisions, which lies, as is argued, in the reliability of the framework for decision-making and in the ability to translate the collaborative participation outputs into actions at different time-frames. Moreover, as the case-study deals with strategic spatial planning, a future oriented approach is needed to warrant the flexibility and robustness of the plan in addressing the uncertainty associated with long term objectives. Those are the critical issues to be handled in the multi-criteria analysis (MCA) framework which sustains the analytical hierarchy process (AHP) that was used to support the decision-making process.publishe