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.