Exploiting the Role of Endogenous Lymphoid-Resident Dendritic Cells in the Priming of NKT Cells and CD8+ T Cells to Dendritic Cell-Based Vaccines

Transfer of antigen between antigen-presenting cells (APCs) is potentially a physiologically relevant mechanism to spread antigen to cells with specialized stimulatory functions. Here we show that specific CD8+ T cell responses induced in response to intravenous administration of antigen-loaded bone marrow-derived dendritic cells (BM-DCs), were ablated in mice selectively depleted of endogenous lymphoid-resident langerin+ CD8α+ dendritic cells (DCs), suggesting that the antigen is transferred from the injected cells to resident APCs. In contrast, antigen-specific CD4+ T cells were primed predominantly by the injected BM-DCs, with only very weak contribution of resident APCs. Crucially, resident langerin+ CD8α+ DCs only contributed to the priming of CD8+ T cells in the presence of maturation stimuli such as intravenous injection of TLR ligands, or by loading the BM-DCs with the glycolipid α-galactosylceramide (α-GalCer) to recruit the adjuvant activity of activated invariant natural killer-like T (iNKT) cells. In fact, injection of α-GalCer-loaded CD1d−/− BM-DCs resulted in potent iNKT cell activation, suggesting that this glycolipid antigen can also be transferred to resident CD1d+ APCs. While iNKT cell activation per se was independent of langerin+ CD8α+ DCs, some iNKT cell-mediated activities were reduced, notably release of IL-12p70 and transactivation of NK cells. We conclude that both protein and glycolipid antigens can be exchanged between distinct DC species. These data suggest that the efficacy of DC-based vaccination strategies may be improved by the incorporation of a systemic maturation signal aimed to engage resident APCs in CD8+ T cell priming, and α-GalCer may be particularly well suited to this purpose

Coaching as an in-school leadership development strategy: experiences from leading from the middle

There is a large literature on leadership mentoring and coaching. However, in education in England, mentoring is the term that has dominated policy and discussion until recently, with the application of this concept as a core element in teacher training and in the induction of new headteachers. Coaching has emerged more recently as a significant element of continuing professional development for teachers. The first national leadership development programme to embody an explicit and systematic approach to coaching was the National College for School Leadership's programme for school middle leaders—Leading from the Middle (LftM). This paper explores the experience of school-based coaching on LftM. It begins by considering key issues concerning the practice of leadership coaching before presenting data on the LftM coaching experience drawn from two evaluations of the programme. The findings suggest that the potential functions of coaches on programmes such as LftM are wider than those in more traditional coaching roles, and the demands arising from the programme and from the school may lead to some role ambiguity. Secondly, three important issues affect the coaching experience: coach skills and commitment, the time devoted to the process, and the place of coaching within broader school leadership development strategies.</p