Because naïve T cells are unable to import cystine due to the absence of cystine transporters, it has been suggested that T cell activation is dependent on cysteine generated by antigen presenting cells. The aim of this study was to determine at which phases during T cell activation exogenous cystine/cysteine is required and how T cells meet this requirement. We found that early activation of T cells is independent of exogenous cystine/cysteine, whereas T cell proliferation is strictly dependent of uptake of exogenous cystine/cysteine. Naïve T cells express no or very low levels of both cystine and cysteine transporters. However, we found that these transporters become strongly up-regulated during T cell activation and provide activated T cells with the required amount of cystine/cysteine needed for T cell proliferation. Thus, T cells are equipped with mechanisms that allow T cell activation and proliferation independently of cysteine generated by antigen presenting cells.
IL-33, an IL-1 family member and ligand for the IL-1 receptor-related protein ST2, has been associated with induction of Th2 cytokines such as IL-4, IL-5, and IL-13. Here, we report that IL-33 can initiate IL-9 protein secretion in vitro in human CD4+ T cells and basophils isolated from peripheral blood. TGF-β has been described as a critical factor for IL-9 induction in Th2 cells; however, we found that TGF-β also induces co-production of IL-9 in purified, naïve (>99%) CD4+CD45RA+CD45RO−CD25− T cells differentiated towards a Th1 profile. Subsequently, it was demonstrated that TGF-β is important, although not an absolute requirement, for IL-9 production in CD4+ T cells. IL-9 production by purified (>95%) human basophils, cultured for 24 h with IL-3 or IL-33, was found, with a strong synergy between the two, likely to be explained by the IL-3 upregulated ST2 expression. Collectively, these data indicate that barrier functioning cells are important for the regulation of IL-9 production by immune cells in inflamed tissue.
Rove beetles of the tribe Quediini are abundant predators in humid microhabitats of forested, open, synanthropic or subterranean ecosystems, with just over 800 species distributed across the temperate and subtropical regions of the Northern Hemisphere. Previous molecular phylogenies included only a limited representation of this diversity but have already indicated that Quedius, containing the majority of Quediini species, is polyphyletic. Six genera, historically associated with Quediini but now Staphylininae incertae sedis, are known only from few pinned specimens and have never been sequenced. Recent synergy between target enrichment phylogenomics, low‐input sequencing of dry, pinned insect specimens and advances in alpha taxonomic knowledge have made comprehensive sampling of Quediini tractable. Here we developed a novel probe set specialized for anchored hybrid enrichment of 1229 single‐copy orthologous loci in Staphylinidae. In one of the largest target enrichment phylogenies of insects to‐date, we sequenced 201 ingroup taxa to clearly delimit monophyletic Quediini within Staphylininae and resolve relationships within this tribe, with 46% of sampled taxa derived from pinned specimens (0–45 years old). Maximum likelihood and coalescent phylogenetic analyses produced well‐resolved, congruent topologies that will serve as a framework for further exploration of this radiation and its necessary generic revision. The inclusion of nearly all remaining Staphylininae incertae sedis genera, all known only from pinned specimens, resulted in the creation of Quelaestrygonini Brunke, trib. n. and revised concepts for Cyrtoquediini and Indoquediini. Quediini was resolved as monophyletic with the transfer of Q. elevatus and Q. nigropolitus to other tribes but Quedius and its subgenera Microsaurus, Distichalius and Raphirus were shown to be para‐ or polyphyletic. Based on the results of our analyses, Velleiopsis Fairmaire, 1882 syn. n. and Megaquedius Casey, 1915 syn. n. are synonymized with Microsaurus Dejean, 1833 resulting in: Q. (Microsaurus) marginiventris (Fairmaire) comb. n., Q. (M.) varendorffi (Reitter) comb.n. Several species of Quedius were transferred from Microsaurus to Distichalius (Q. aethiops Smetana, Q. biann Smetana, Q. cingulatus Smetana and Q. taruni Smetana), Distichalius to Raphirus (Q. fagelianus Scheerpeltz) and Microsaurus to Raphirus (Q. mixtus Eppelsheim and Q. persicus Korge).
The CD3γ di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3γ di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8+ T cells is impaired in mice with a mutated CD3γ di-leucine-based motif. The CD3γ mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8+ T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3γ-mediated TCR down-regulation in virus-specific CD8+ T cell responses.
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