Jens Geginat showed that the CCR6+IL-7Rhi T-cell population contains not only Th17 cells but also memory cells that secrete suppressive IL-10 upon suboptimal TCR stimulation and with autologous DC; however, the same cells also produce CD40L, IFN-γ, and IL-2 following optimal TCR stimulation and with a relevant recall antigen, which is similar to the response of conventional memory T cells, suggesting that the cells have a context-dependent regulatory function. A subset of IL-10-producing Th1 effector cells, which suppress T-cell proliferation by an IL-10-dependent mechanism, was also identified in the CD4+CD25−IL-7Rlo T-cell

population. These effector cells express high levels of CTLA-4, and are anergic in vitro but proliferate in vivo presumably in response to persistent antigens. mTOR inhibitor As the identified memory and effector-like T-cell subsets show different requirements, kinetics, and stabilities of IL-10 production, Jens Geginat proposed that they have different functions and might inhibit different types of immune responses. Naturally occurring regulatory T cells (Tregs)

have been shown to control immune responses to self and non-self. Muriel Moser (Brussels, Belgium) discussed the regulation of Th1 cells by naturally occurring and adaptive Tregs. It has previously been shown Copanlisib in vivo that depletion of natural Treg before immunization with antigen-pulsed dendritic cells (DC) results in increased Th1-type responses characterized by high levels of IFN-γ production and CTL activity. The mechanism by which Tregs control the development of Th1-like responses, including the role of two Th1-prone factors, IL-12 and CD70, has also been examined. In vivo Treg depletion was found to lead to increased IFN-γ production in both wild-type and IL-12 p40-deficient mouse strains, suggesting that the ability of Tregs to down-modulate Th1 responses is largely IL-12- and IL-23-independent. 4��8C In marked contrast, neutralizing antibodies to CD70, a membrane-associated TNF family member, prevented the ability of Treg depletion to increase IFN-γ production. In vitro experiments

demonstrated that Tregs inhibit CD70 expression in a contact-dependent manner and, although the suppressive mechanism is still unclear, it may involve a phenomenon of (trans)-endocytosis because CD27−/− Tregs failed to downregulate CD70 in vitro. These observations indicate that natural Tregs control Th1 cell development by predominantly interfering with the CD70/CD27 pathway. Tomáš Brdička (Prague, Czech Republic) presented new data on the regulation of Src-family kinases (SFKs) in leukocytes. SFKs are regulated by phosphorylation of their inhibitory and activatory tyrosines, with the outcome depending on the complex interplay between the activities of several phosphatases, kinases, and adaptor proteins.

Granulocytes are generally considered effector cells of the innate immune response (46).

The importance of each of these cell types (i.e. RCs, MCs and neutrophils) therefore is worth considering in the context of the current study. Recent studies on both wild and farmed fish suggest that RCs represent an immune cell type closely linked to other piscine inflammatory cells (45,47). RCs are found exclusively in fish in a wide range of tissues and are commonly associated with epithelia (23). As M. wageneri destroys the epithelia at the site of attachment, it was not possible to compare the number of RCs in uninfected and parasitized tench. The presence of RCs in the intestinal submucosa of infected tench and those in direct contact with the blood vessels is interesting and suggests that

RCs also use the circulatory system to migrate to the site of infection. Similar findings have been reported ALK phosphorylation for fish that were infected with acanthocephalans (10,48). Fish MCs, also known as eosinophilic granule cells, have cytochemical features, functional properties and tissue locations that have led to the suggestion that they are analogous to mammalian MCs (22,23,25). Several published reports on the intratissue migratory nature of MCs suggest that fish may have two populations of MCs, one circulating and one resident, and that the presence of parasites induces the recruitment of MCs to the site of infection (25,28). The significantly higher number of MCs found at the site of parasite attachment, CYC202 price when compared to uninfected tench, in MycoClean Mycoplasma Removal Kit the current study supports similar results reported for other fish–helminth systems (48). In teleosts, considerable descriptive data exist showing how MCs degranulate in response to a variety of known degranulating agents (49) and pathogens (23,25,30). In parasitized tench, an intense degranulation of MCs was seen at the site of tapeworm infection, notably in the immediate zone surrounding the scolex.

It is likely that the secretions produced by the MCs may have a role in attracting other cell types (i.e. neutrophils) involved in the inflammatory process, particularly during the period of initial pathogen challenge (24,32). One study reported that intra-epithelial MCs are present in low numbers in healthy epithelium but then dramatically increase in number with certain parasitic infections (50). In the current study, MCs, in the intestines of parasitized tench, were frequently observed among epithelial cells. Neutrophils are among the first cell types to arrive at the sites of inflammation and play a critical role in the teleost innate immune defence system (31). In infected tench, numerous neutrophils were observed to co-occur with MCs in the submucosa at the sites of M. wageneri attachment. A similar observation was found in the livers of minnows, Phoxinus phoxinus (L.