We also suggest that these

migrating Treg lymphocytes could be hsp-specific T cells. These cells exert their regulatory effect when exposed to hsp, which is a stress protein and could therefore be up-regulated at the inflammatory site [9]. Altogether, these results showed that the prime-boost procedure protected NOD mice against diabetes and that this strategy was even more effective than BCG alone, as suggested by diabetes incidence findings. Further investigation will allow us to determine if Treg cells are really located in the pancreas and if these cells are hsp-specific, as we are proposing. Interestingly, the protective effects observed in NOD mice were not detected in the MLD–STZ model. This finding was unexpected and differ, to some extent, from

what has been suggested EGFR activation by a few papers. There is only one report where the authors demonstrated that a BCG vaccine prevented insulitis in MLD–STZ diabetes in mice [12]. However, a direct comparison with the present work is hardly possible because distinct protocols, including mouse strain, timing and the BCG immunization route, were adopted. In addition, two other studies showed that vaccination with a heat shock protein (hsp65) was able to protect mice against diabetes induced by STZ [19, 22]. Considering that the click here prime-boost strategy was able to decrease significantly the severity of insulitis and to avoid hyperglycaemia in NOD mice, we are tempted to attribute the observed failure to the STZ model itself. These two diabetes type 1 models present characteristics that could account for their 6-phosphogluconolactonase distinct behaviour. The

NOD mouse has been considered to be the model that resembles human type 1 diabetes most accurately in its genetic and immunopathogenic complexity [23, 24]. For this reason it has been the preferred choice in investigating the role played by different T cell subsets in insulitis [25, 26] and also to explore treatment strategies that target the autoimmune process [27, 28]. The MLD–STZ is also considered a type 1 diabetes model in which the contribution of macrophages, Th subsets and Tc cells have been characterized [19, 29, 30]. However, STZ can induce diabetes even in the absence of T and B cells, suggesting that it does not model the human pathology as closely as the disease developed by NOD mice [31]. This model is indicated preferentially to pursue therapies targeting cytokines and oxidants and also approaches to prevent beta cell death [28, 32]. The need to use a toxic diabetogenic drug could also contribute to the inefficacy of BCG/pVAXhsp65 over the STZ model. The current view is that STZ determines strong immunosuppression associated with significant lymphopenia [33]. A direct effect of this drug over the immune system has been ascertained in vitro and in vivo [34, 35].