A large proportion of bovine T cells express the γδ T cell receptor and show a distinct tissue distribution and surface phenotype

The numbers, phenotype, and tissue distribution of γδ T cells in cattle were studied using two monoclonal antibodies (mAbs) which react with the bovine γδ T cell receptor (TCR). Both mAbs stained 20-40% of T cells in peripheral blood, and immunoprecipitated molecules of 44 and 36 kd (reduced) and 70-80 kd (non-reduced). In cattle the majority of circulating γδ T cells showed a distinct surface phenotype; they expressed T19, a 215 kd molecule described in sheep and cattle which marks only γδ T cells. Bovine γδ T cells were also CD2−, CD4−, and mostly CD8−, and falled to express CD6, a molecule possibly involved in T cell activation. The distribution of γδ T cells in cattle lymphoid tissues differed markedly from that in humans, in that bovine γδ T cells were concentrated around lymph node trabeculae and were usually sparse or absent from the B cell and T cell domains of lymph nodes. Like most other species studied, γδ T cells in cattle were localized to epithelial surfaces, particularly within the skin and intestine, indicating that it was at these sites where γδ T cells functioned. Our results provide further evidence for the unusual localization, recirculation pattern, and phenotype of γδ T cells, and also show that some features of γδ T cells can differ quite markedly from species to specie

Diet, Metabolites, and “Western-Lifestyle” Inflammatory Diseases

One explanation for the increased incidence of allergies, asthma, and even some autoimmune diseases has been the hygiene hypothesis. However, recent studies also highlight an important role for diet and bacterial metabolites in controlling various immune pathways, including gut and immune homeostasis, regulatory T cell biology, and inflammation. Dietary-related metabolites engage “metabolite-sensing” G-protein-coupled receptors, such as GPR43, GPR41, GPR109A, GPR120, and GPR35. These receptors are expressed on immune cells and some gut epithelial cells and generally mediate a direct anti-inflammatory effect. Insufficient intake of “healthy foodstuffs” adversely affects the production of bacterial metabolites. These metabolites and those derived directly from food drive beneficial downstream effects on immune pathways. We propose that insufficient exposure to dietary and bacterial metabolites might underlie the development of inflammatory disorders in Western countries. This review highlights what is currently known about diet, metabolites, and their associated immune pathways in relation to the development of inflammatory disease

A fundamental bimodal role for neuropeptide Y1 receptor in the immune system

Psychological conditions, including stress, compromise immune defenses. Although this concept is not novel, the molecular mechanism behind it remains unclear. Neuropeptide Y (NPY) in the central nervous system is a major regulator of numerous physiological functions, including stress. Postganglionic sympathetic nerves innervating lymphoid organs release NPY, which together with other peptides activate five Y receptors (Y1, Y2, Y4, Y5, and y6). Using Y1-deficient (Y1−/−) mice, we showed that Y1−/− T cells are hyperresponsive to activation and trigger severe colitis after transfer into lymphopenic mice. Thus, signaling through Y1 receptor on T cells inhibits T cell activation and controls the magnitude of T cell responses. Paradoxically, Y1−/− mice were resistant to T helper type 1 (Th1) cell–mediated inflammatory responses and showed reduced levels of the Th1 cell–promoting cytokine interleukin 12 and reduced interferon γ production. This defect was due to functionally impaired antigen-presenting cells (APCs), and consequently, Y1−/− mice had reduced numbers of effector T cells. These results demonstrate a fundamental bimodal role for the Y1 receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function. Our findings uncover a sophisticated molecular mechanism regulating immune cell functions that can lead to stress-induced immunosuppression

Guidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses

SummaryHumoral immunity depends on both rapid and long-term antibody production against invading pathogens. This is achieved by the generation of spatially distinct extrafollicular plasmablast and follicular germinal center (GC) B cell populations, but the signals that guide responding B cells to these alternative compartments have not been fully elucidated. Here, we show that expression of the orphan G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) by activated B cells was essential for their movement to extrafollicular sites and induction of early plasmablast responses. Conversely, downregulation of EBI2 enabled B cells to access the center of follicles and promoted efficient GC formation. EBI2 therefore provides a previously uncharacterized dimension to B cell migration that is crucial for coordinating rapid versus long-term antibody responses

Expression of CD44 molecules and CD44 ligands during human thymic fetal development: expression of CD44 isoforms is developmentally regulated

It has recently been recognized that CD44 comprises a large family of alternatively spliced forms.In the thymus, CD44 has been postulated to play an important role in immature T cell migration and maturation. In this paper, we have studied the expression of CD44 molecules and two CD44 ligands, hyaluronan (HA) and fibronectin (FN), during human thymic fetal development. We found that mAbs against all CD44 isoforms (A3D8 or A1G3) reacted with both thymic epithelial (TE) cells and thymocytes beginning at the time of initial colonization of the human thymus by hematopoietic stem cells at 8.2 weeks of fetal gestation. However, mAbs specific for splice variants of CD44 containing membrane-proximal inserts (11.24, 11.10 and 11.9) reacted only with terminally differentiated TE cells in and around Hassall's bodies beginning at 16-19 weeks of fetal gestation. Studies of differentiated versus undifferentiated TE cells in vitro confirmed the selective expression of CD44 variant isoforms on terminally differentiated TE cells. Expression of HA and FN was determined by fluorescence microscopy using either biotlnylated-HA binding protein or an anti-FN mAb. We found that whereas FN was present throughout the human fetal thymus beginning at 8.2 weeks, HA was not present until 16 weeks of gestational age. These data demonstrate the differential expression of standard versus variant CD44 isoforms during thymic ontogeny and implicate CD44 interactions with ligands other than HA as important in the earlier stages of humanthymus developmen

Piecewise Linear Models for the Quasiperiodic Transition to Chaos

We formulate and study analytically and computationally two families of piecewise linear degree one circle maps. These families offer the rare advantage of being non-trivial but essentially solvable models for the phenomenon of mode-locking and the quasi-periodic transition to chaos. For instance, for these families, we obtain complete solutions to several questions still largely unanswered for families of smooth circle maps. Our main results describe (1) the sets of maps in these families having some prescribed rotation interval; (2) the boundaries between zero and positive topological entropy and between zero length and non-zero length rotation interval; and (3) the structure and bifurcations of the attractors in one of these families. We discuss the interpretation of these maps as low-order spline approximations to the classic ``sine-circle'' map and examine more generally the implications of our results for the case of smooth circle maps. We also mention a possible connection to recent experiments on models of a driven Josephson junction.Comment: 75 pages, plain TeX, 47 figures (available on request

Modelling quasicrystals at positive temperature

We consider a two-dimensional lattice model of equilibrium statistical mechanics, using nearest neighbor interactions based on the matching conditions for an aperiodic set of 16 Wang tiles. This model has uncountably many ground state configurations, all of which are nonperiodic. The question addressed in this paper is whether nonperiodicity persists at low but positive temperature. We present arguments, mostly numerical, that this is indeed the case. In particular, we define an appropriate order parameter, prove that it is identically zero at high temperatures, and show by Monte Carlo simulation that it is nonzero at low temperatures