Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse

Expression of the T Cell Receptor αβ on a CD123+ BDCA2+ HLA-DR+ Subpopulation in Head and Neck Squamous Cell Carcinoma

Human Plasmacytoid Dendritic Cells (PDCs) infiltrating solid tumor tissues and draining lymph nodes of Head and Neck Squamous Cell Carcinoma (HNSCC) show an impaired immune response. In addition to an attenuated secretion of IFN-α little is known about other HNSCC-induced functional alterations in PDCs. Particular objectives in this project were to gain new insights regarding tumor-induced phenotypical and functional alterations in the PDC population. We showed by FACS analysis and RT-PCR that HNSCC orchestrates an as yet unknown subpopulation exhibiting functional autonomy in-vitro and in-vivo besides bearing phenotypical resemblance to PDCs and T cells. A subset, positive for the PDC markers CD123, BDCA-2, HLA-DR and the T cell receptor αβ (TCR-αβ) was significantly induced subsequent to stimulation with HNSCC in-vitro (p = 0.009) and also present in metastatic lymph nodes in-vivo. This subgroup could be functionally distinguished due to an enhanced production of IL-2 (p = 0.02), IL-6 (p = 0.0007) and TGF-β (not significant). Furthermore, after exposure to HNSCC cells, mRNA levels revealed a D-J-beta rearrangement of the TCR-beta chain besides a strong enhancement of the CD3ε chain in the PDC population. Our data indicate an interface between the PDC and T cell lineage. These findings will improve our understanding of phenotypical and functional intricacies concerning the very heterogeneous PDC population in-vivo

Cell Lineages and the Logic of Proliferative Control

It is widely accepted that the growth and regeneration of tissues and organs is tightly controlled. Although experimental studies are beginning to reveal molecular mechanisms underlying such control, there is still very little known about the control strategies themselves. Here, we consider how secreted negative feedback factors (“chalones”) may be used to control the output of multistage cell lineages, as exemplified by the actions of GDF11 and activin in a self-renewing neural tissue, the mammalian olfactory epithelium (OE). We begin by specifying performance objectives—what, precisely, is being controlled, and to what degree—and go on to calculate how well different types of feedback configurations, feedback sensitivities, and tissue architectures achieve control. Ultimately, we show that many features of the OE—the number of feedback loops, the cellular processes targeted by feedback, even the location of progenitor cells within the tissue—fit with expectations for the best possible control. In so doing, we also show that certain distinctions that are commonly drawn among cells and molecules—such as whether a cell is a stem cell or transit-amplifying cell, or whether a molecule is a growth inhibitor or stimulator—may be the consequences of control, and not a reflection of intrinsic differences in cellular or molecular character

Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby

Background: The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby.Results: We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor diversity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed.Conclusion: This is the first study comparing the transcriptomes of two thymuses from a single individual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system

Quantitative and qualitative influences of tapasin on the class I peptide repertoire

C1 - Journal Articles RefereedTapasin is critical for efficient loading and surface expression of most HLA class I molecules. The high level surface expression of HLA-B*2705 on tapasin-deficient 721.220 cells allowed the influence of this chaperone on peptide repertoire to be examined. Comparison of peptides bound to HLA-B*2705 expressed on tapasin-deficient and -proficient cells by mass spectrometry revealed an overall reduction in the recovery of B*2705-bound peptides isolated from tapasin-deficient cells despite similar yields of B27 heavy chain and beta(2)-microglobulin. This indicated that a proportion of suboptimal ligands were associated with B27, and they were lost during the purification process. Notwithstanding this failure to recover these suboptimal peptides, there was substantial overlap in the repertoire and biochemical properties of peptides recovered from B27 complexes derived from tapasin-positive and -negative cells. Although many peptides were preferentially or uniquely isolated from B*2705 in tapasin-positive cells, a number of species were preferentially recovered in the absence of tapasin, and some of these peptide ligands have been sequenced. In general, these ligands did not exhibit exceptional binding affinity, and we invoke an argument based on lumenal availability and affinity to explain their tapasin independence. The differential display of peptides in tapasin-negative and -positive cells was also apparent in the reactivity of peptide-sensitive alloreactive CTL raised against tapasin-positive and -negative targets, demonstrating the functional relevance of the biochemical observation of changes in peptide repertoire in the tapasin-deficient APC. Overall, the data reveal that tapasin quantitatively and qualitatively influences ligand selection by class I molecules

Ikskile’s transformations and their reflections in virtual space

Maģistra darba „Ikšķiles transformācijas un to atspoguļojums virtuālā telpā” mērķis ir noskaidrot vietas transformācijas izpausmes Ikšķiles pilsētā un lauku teritorijā, kā arī analizēt to cilvēku uztverē un atspoguļojumu virtuālā telpā. Maģistra darba tēmas izvēle ir saistīta ar Ikšķiles kā vietas un telpas straujo attīstību Rīgas pilsētas pievārtē, pieaugošo moderno tehnoloģiju lomu cilvēku ikdienā, kā arī ar autora profesionālo darbību Ikšķiles novadā - gandrīz desmit gadus autors ir strādājis mērniecības jomā. Maģistra darbs rakstīts ar mērķi izpētīt vietas transformācijas izpausmes no cilvēka ģeogrāfijas konceptuālā skatījuma, lielo pilsētu reģionu ietekmē, analizēt ietekmes un atspoguļojumu virtuālā telpā.Master`s thesis „ Ikskile’s transformations and their reflections in virtual space” purpose is to elucidate expressions of place transformations in Ikskile and rural areas, analyze the perception of space transformations and it`s reflections in virtual space. The Masters theme is based on Ikskile`s space rapid development on the outskirts of Riga and the increasing role of modern technologies in everyday life. Based on the experience of the author`s professional activities in Ikskile – nearly ten years author has worked in the sphere of field surveying. The Masters Paper aim is to explore place transformations expressions from conceptual view of human geography, taking into context the influence of growth and development of major urban areas, analyze impact and reflections in virtual space