This finding contrasts with observations in another parasitic infection model (14,15), suggesting an important role for the β-chymase mMCP-1 in impairing intestinal permeability (19). Most likely, this contrast is because of differences in excretion mechanisms between the different species of parasites, related to their specific niches. Furthermore,
the reported severe reduction in the secretory capacity of the epithelium during schistosomiasis PR171 shows that the mechanisms facilitating passage of schistosoma eggs through the mouse gut wall are directed not only at the TJs, but most particularly at the epithelial cells proper. This work was supported by FWO-grant G.0377·04 (to JPT and EVM), a RAFO project (CF 114070 to LVN) and a GOA (concerted research action)-grant (to JPT) of the University of Antwerp. A. B. A. Kroese is holder of a guest professorship click here at the University of Antwerp. The authors thank the technical staff of all laboratories for excellent assistance.
We especially thank L. Svensson for expert technical assistance with the tissue and faecal egg count. “
“CD4-mediated T-cell help in the activation of CD8+ T cells and B cells, through linked-recognition of antigenic determinants, is a long-standing concept foundational to our understanding of immunity (presence of help) versus tolerance (lack of help). Surprisingly, this function of CD4+ T cells has not been extensively examined as a means to overcome immune tolerance of the self-antigens made by tumor cells. Hesitation to employ this powerful mechanism may be due to the potential to cause unwanted autoimmune pathology. In this issue of the European Journal of Immunology, Snook et al. [Eur. J. Immunol. 2014. ADP ribosylation factor 44:
1956–1966] identify a state of split tolerance, showing that CD4+ T cells specific for a number of tumor-associated self-antigens are robustly tolerant, while their CD8+ T-cell and B-cell counterparts are far less tolerant. Furthermore, the authors demonstrate that provision of linked foreign helper epitopes, such as influenza hemagglutinin, substantially enhances both CD8+ T-cell and B-cell responses to tumor self-antigens without causing any overt autoimmune pathology. These findings provide a strong rationale to employ foreign helper epitopes in cancer vaccines and highlight the need to fully explore therapeutic strategies that are based on well-established immunologic concepts. Tumor immunotherapy has, in recent years, enjoyed a renaissance since it has begun to achieve some of its long anticipated goals in the clinical setting .