Non-Canonicaly Recruited TCRαβCD8αα IELs Recognize Microbial Antigens

In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα+ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα+ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα+ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα+ IELs and CD4+ T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα+ IELs and CD4+ derived T cell hybridomas suggesting that some of TCRαβCD8αα+ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4+ IELs and Foxp3CD4+ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3CNS1 sufficient or Foxp3CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα+ in small intestine expends in situ in response to changes in microbial flora

Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation

The diversion of MHC class II-restricted thymocytes into the regulatory T (Treg) cell lineage, similarly to clonal deletion, is driven by intrathymic encounter of agonist self-antigens. Somewhat paradoxically, it thus seems that the expression of an autoreactive T cell receptor is a shared characteristic of T cells that are subject to clonal deletion and those that are diverted into the Treg cell lineage. Here, we discuss how thymocyte-intrinsic and -extrinsic determinants may specify the choice between these two fundamentally different T cell fates

Re-evaluating the Quoit Brooch Style: Economic and Cultural Transformations in the 5th Century ad, with an Updated Catalogue of Known Quoit Brooch Style Artefacts

Quoit Brooch Style material, produced from the early 5th century onwards, has previously been considered mostly from a stylistic point of view, leaving much scope for further investigation. In addition, the known corpus of material has been much expanded through newly excavated and metal-detected finds. In this article, I bring together the known extant material for the first time, and document important evidence relating to contextual dating, gender associations, manufacture (including new compositional analysis of c 75 objects), repair, and reuse. The article questions previous interpretations of Quoit Brooch Style material relating to Germanic mercenaries and/or post-Romano-British political entities. It interprets the earliest material as part of wider trends elsewhere, in Britain and in Continental northwestern Europe, for the production of material imitating late Roman symbols of power. It presents new evidence for connectivity with Continental Europe via the western Channel route in the 5th century. A detailed investigation of individual artefacts shows that many Quoit Brooch Style objects were reused, sometimes being subjected to extensive repair and modification. This provides new insights into the 5th century metal economy, for instance, acute problems in the availability of new metal objects in southeastern Britain in the middle years of the 5th century. Compositional analysis contributes further to our understanding of metal supply in the 5th century and relationships with the post-Roman West. Insights are provided into wider cultural transformations in the 5th century and the gradual loss of value that occurred for Roman-style objects

Tissue response to the components of a hydroxyapatite-coated composite femoral implant

Bone loss around femoral implants used for THA is a persistent clinical concern. It may be caused by stress shielding, generally attributed to a mismatch in stiffness between the implants and host bone. In this regard, a fatigue resistant, carbon fiber (CF) composite femoral implant with bone-matching stiffness has been developed. This study evaluated the tissue response to the three material components of this implant in normal and textured (blasted with 24 grit alumina) surfaces: the hydroxyapatite (HA) coating, the CF composite and the intermediate crystalline HA particulate composite layer to bond to the HA coating (blended). Sprague-Dawley rats underwent bilateral femoral implantation each receiving two rod-like implants. Bone apposition to the HA (37%) and textured Ti (41%) implants was not significantly different. Bone apposition to the untextured CF (14%) and blended (19%) implants and polished Ti (8%) implants was significantly lower. Bone apposition to the textured CF (9%) and blended (11%) implants was lower (but not statistically from the as received or untextured counterparts). Nearly all sections from femurs containing CF implants presented CF debris. There was no evidence of localized bone loss or any strong immune response associated with any of the implant materials. All materials were well tolerated with minimal inflammation despite the presence of particulate debris. The high degree of bone apposition to the HA-coated composite implants and the lack of short-term inflammation and adverse tissue response to the three material implant component support continued evaluation of this composite technology for use in THA.Peer reviewed: YesNRC publication: Ye

Biomimetic HA-coated Composite Hip Implants and Cell Adhesion

Peer reviewed: YesNRC publication: Ye