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Discusses research being done on the role of Calcineurin B1 for positive but not negative selection of developing T cells during thymic development. Reference to a study made by J. R. Neilson, which was published in the 2004 issue of the journal "Immunity"; Process that occurs before T cells emigrate from the thymus; Mechanism by which low-intensity interactions result in cell survival and proliferation and high-intensity interactions result in cell death.

Molecular automata are mixtures of molecules that undergo precisely defined structural changes in response to sequential interactions with inputs. Previously studied nucleic acid-based automata include game-playing molecular devices (MAYA automata) and finite-state automata for the analysis of nucleic acids, with the latter inspiring circuits for the analysis of RNA species inside cells. Here, we describe automata based on strand-displacement cascades directed by antibodies that can analyse cells by using their surface markers as inputs. The final output of a molecular automaton that successfully completes its analysis is the presence of a unique molecular tag on the cell surface of a specific subpopulation of lymphocytes within human blood cells. [ABSTRACT FROM AUTHOR]

The inhibitory immunoregulatory receptor CTLA-4 is critical in maintaining self-tolerance, but the mechanisms of its actions have remained controversial. Here we examined the antigen specificity of tissue-infiltrating CD4+ T cells in Ctla4−/− mice. After adoptive transfer, T cells isolated from tissues of Ctla4−/− mice showed T cell antigen receptor (TCR)-dependent accumulation in the tissues from which they were derived, which suggested reactivity to tissue-specific antigens. We identified the pancreas-specific enzyme PDIA2 as an autoantigen in Ctla4−/− mice. CTLA-4 expressed either on PDIA2-specific effector cells or on regulatory T cells was sufficient to control tissue destruction mediated by PDIA2-specific T cells. Our results demonstrate that both cell-intrinsic and non–cell-autonomous actions of CTLA-4 operate to maintain T cell tolerance to a self antigen. [ABSTRACT FROM AUTHOR]

Presents research which proves that the strength of the signal transmitted by the T-cell receptor (TCR) is the key determinant in the αβ/γδ lineage-fate decision. Role of T-cell receptor in αβ/γδ lineage commitment; Results of the experiment done in the study;Difference between γδ TCR thymocytes and pre-TCR thymocytes.

CD4+ T helper cells are well known for their role in providing critical signals during priming of cytotoxic CD8+ T lymphocyte (CTL) responses in vivo. T-cell help is required for the generation of primary CTL responses as well as in promoting protective CD8+ memory T-cell development. However, the role of CD4 help in the control of CTL responses at the effector stage is unknown. Here we show that fully helped effector CTLs are themselves not self-sufficient for entry into the infected tissue, but rely on the CD4+ T cells to provide the necessary cue. CD4+ T helper cells control the migration of CTL indirectly through the secretion of IFN-γ and induction of local chemokine secretion in the infected tissue. Our results reveal a previously unappreciated role of CD4 help in mobilizing effector CTL to the peripheral sites of infection where they help to eliminate infected cells. [ABSTRACT FROM AUTHOR]

The adaptors SAP, EAT-2 and ERT are specific to cells of the immune system and belong to the SAP family. All three are expressed in natural killer (NK) cells. Here we examined the global function of the SAP family using mice lacking SAP, EAT-2 and ERT. These adaptors acted together in a mechanism that was essential for the elimination of hematopoietic but not nonhematopoietic cells by NK cells. This function was mediated by many receptors of the SLAM family on NK cells that were engaged by ligands found solely on hematopoietic cells. In the absence of SAP-related adaptors, SLAM receptors lost their activating function and became inhibitory receptors that repressed other activating receptors, such as NKG2D. Hence, the SAP family is essential for the elimination of unwanted hematopoietic cells by NK cells. [ABSTRACT FROM AUTHOR]

Introduction: Chronic inflammation at the cardia occurs in gastroesophageal reflux disease (GERD), as well as in the presence of Helicobacter pylori. Regulatory T cells have been demonstrated for H. pylori-induced gastritis, whereas their role has not been studied in GERD.Methods: We prospectively analyzed the expression of FOXP3, a marker of various regulatory T cells, as well as the mucosal transcript levels of TGF-beta1 and IL-10. RNA and protein levels have been determined in cardiac biopsies of 70 patients stratified according to GERD (n = 22), controls (n = 17), and H. pylori (n = 31).Results: GERD presented with chronic inflammation and reduced FOXP3-mRNA in the cardiac mucosa (-84%), whereas H. pylori-positive patients revealed a 25.1-fold increase of FOXP3 gene expression. These results were verified by the regulatory cytokines IL-10 and TGF-beta1, and by the immunohistochemical detection of intramucosal FOXP3-expressing T cells.Conclusion: Chronic inflammation at the cardia associated with either GERD or H. pylori differs concerning the presence of FOXP3-expressing T cells. In contrast to H. pylori, FOXP3-expressing T cells are not associated with GERD-associated carditis. [ABSTRACT FROM AUTHOR]

Abstract  Acidic mucins such as sialomucin and sulfomucin produced by intestinal epithelial cells have been implicated in the protection of the mucosa from pathogens. In the present study, we analyzed the alteration of acidic mucins in the jejunum of euthymic and athymic rats infected with the nematode Nippostrongylus brasiliensis using alcian blue staining and a high iron-diamine method. The numbers of sialomucin goblet cells increased markedly 7 and 10 days post-infection and decreased gradually thereafter in euthymic rats, while athymic rats did not show sialomucin goblet cell hyperplasia at least until 28 days post-infection, suggesting that sialomucin production might be regulated by thymus-derived T cells. On the other hand, the numbers of sulfomucin goblet cells increased markedly 28 days post-infection in both euthymic and athymic rats despite the fact that sulfomucin goblet cell numbers in uninfected athymic rats were significantly smaller than in euthymic rats. Real-time polymerase chain reaction studies on the gene transcription levels of O-glycan sulfotransferases Gal3ST1, Gal3ST2, Gal3ST3, and Gal3ST4 in the jejunal epithelium increased gradually toward day 28 post-infection in euthymic and athymic rats. These results suggest that the production of sulfomucin and expression of Gal3STs are inducible by nematode infection without the activation of thymus-derived T cells. [ABSTRACT FROM AUTHOR]

T helper cells that produce IL-17 (TH17 cells) promote autoimmunity in mice and have been implicated in the pathogenesis of human inflammatory diseases. At mucosal surfaces, TH17 cells are thought to protect the host from infection, whereas regulatory T (Treg) cells control immune responses and inflammation triggered by the resident microflora. Differentiation of both cell types requires transforming growth factor-β (TGF-β), but depends on distinct transcription factors: RORγt (encoded by Rorc(γt)) for TH17 cells and Foxp3 for Treg cells. How TGF-β regulates the differentiation of T cells with opposing activities has been perplexing. Here we demonstrate that, together with pro-inflammatory cytokines, TGF-β orchestrates TH17 cell differentiation in a concentration-dependent manner. At low concentrations, TGF-β synergizes with interleukin (IL)-6 and IL-21 (refs 9–11) to promote IL-23 receptor (Il23r) expression, favouring TH17 cell differentiation. High concentrations of TGF-β repress IL23r expression and favour Foxp3+ Treg cells. RORγt and Foxp3 are co-expressed in naive CD4+ T cells exposed to TGF-β and in a subset of T cells in the small intestinal lamina propria of the mouse. In vitro, TGF-β-induced Foxp3 inhibits RORγt function, at least in part through their interaction. Accordingly, lamina propria T cells that co-express both transcription factors produce less IL-17 (also known as IL-17a) than those that express RORγt alone. IL-6, IL-21 and IL-23 relieve Foxp3-mediated inhibition of RORγt, thereby promoting TH17 cell differentiation. Therefore, the decision of antigen-stimulated cells to differentiate into either TH17 or Treg cells depends on the cytokine-regulated balance of RORγt and Foxp3. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor best known for mediating the toxicity of dioxin. Environmental factors are believed to contribute to the increased prevalence of autoimmune diseases, many of which are due to the activity of TH17 T cells, a new helper T-cell subset characterized by the production of the cytokine IL-17. Here we show that in the CD4+ T-cell lineage of mice AHR expression is restricted to the TH17 cell subset and its ligation results in the production of the TH17 cytokine interleukin (IL)-22. AHR is also expressed in human TH17 cells. Activation of AHR by a high-affinity ligand during TH17 cell development markedly increases the proportion of TH17 T cells and their production of cytokines. CD4+ T cells from AHR-deficient mice can develop TH17 cell responses, but when confronted with AHR ligand fail to produce IL-22 and do not show enhanced TH17 cell development. AHR activation during induction of experimental autoimmune encephalomyelitis causes accelerated onset and increased pathology in wild-type mice, but not AHR-deficient mice. AHR ligands may therefore represent co-factors in the development of autoimmune diseases. [ABSTRACT FROM AUTHOR]

The conventional wisdom is that cell-surface receptors interact with ligands expressed on other cells to mediate cell-to-cell communication (trans interactions). Unexpectedly, it has recently been found that two classes of receptors specific for MHC class I molecules not only interact with MHC class I molecules expressed on opposing cells, but also with those on the same cell. These cis interactions are a feature of immunoreceptors that inhibit, rather than activate, cellular functions. Here, we review situations in which cis interactions have been observed, the characteristics of receptors that bind in trans and cis, and the biological roles of cis recognition. [ABSTRACT FROM AUTHOR]

Focuses on the discovery of a B-cell signalling pathway in New Delhi, India. Activation of antigen in T-cell areas of lymphoid tissues; Analysis on signalling pathways in the differentiation of resting B cells to GC B cells; Inhibition mechanisms of protein kinase A.

On activation, T cells undergo distinct developmental pathways, attaining specialized properties and effector functions. T-helper (TH) cells are traditionally thought to differentiate into TH1 and TH2 cell subsets. TH1 cells are necessary to clear intracellular pathogens and TH2 cells are important for clearing extracellular organisms. Recently, a subset of interleukin (IL)-17-producing T (TH17) cells distinct from TH1 or TH2 cells has been described and shown to have a crucial role in the induction of autoimmune tissue injury. In contrast, CD4+CD25+Foxp3+ regulatory T (Treg) cells inhibit autoimmunity and protect against tissue injury. Transforming growth factor-β (TGF-β) is a critical differentiation factor for the generation of Treg cells. Here we show, using mice with a reporter introduced into the endogenous Foxp3 locus, that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β. We also demonstrate that IL-23 is not the differentiation factor for the generation of TH17 cells. Instead, IL-6 and TGF-β together induce the differentiation of pathogenic TH17 cells from naive T cells. Our data demonstrate a dichotomy in the generation of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T cells that inhibit autoimmune tissue injury. [ABSTRACT FROM AUTHOR]

CARMA1, BCL-10 and MALT1 are signalling proteins that have a key role in antigen-receptor-mediated lymphocyte activation through the nuclear factor-?B pathway. Recent genetic studies have revealed additional, previously unexpected roles for these proteins in the development of B and T cells, and in the CD40- and lipopolysaccharide-dependent activation of B cells. Here, I discuss recent advances in the understanding of the molecular and biological functions of these proteins. [ABSTRACT FROM AUTHOR]

A two-dimensional (2D) slice of a 3D hemispherical acoustic Luneburg lens using a quasi-conformal transformation and face-centred-orifice-cubic (FCOC) unit cells is designed and fabricated. With the system, the focusing characteristics of acoustic waves with frequencies that satisfy the homogeneous medium condition of the metamaterial are observed, such as focusing of acoustic plane waves at the antipodal point on the transformed surface of the opposite side for the incident direction and focus spreading due to total internal reflection at the focus point. The attenuation losses of the system are measured and compared with those of an untransformed system with respect to frequency. The value of the acoustic Goos–Hänchen shift is determined by comparing the experimental and theoretical and simulated values of the focus points with respect to the incident angle. The effect of acoustic Fresnel filtering due to the angular distribution of the incident waves at the flat surface boundary is verified by comparing the results of the experiment and a simulation. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as additional protein and carbohydrate components. Proteoglycans (PGs) contribute to the heterogeneity of the ECM and play an important role in its structure and function. While the small leucine rich proteoglycans (SLRPs), including decorin and lumican, have been studied extensively as mediators of collagen fibrillogenesis and organization, the function of large matrix PGs in collagen matrices is less well known. In this study, we showed that different matrix PGs have distinct roles in regulating collagen behaviors. We found that versican, a large chondroitin sulfate PG, promotes collagen fibrillogenesis in a turbidity assay and upregulates cell-mediated collagen compaction and reorganization, whereas aggrecan, a structurally-similar large PG, has different and often opposing effects on collagen. Compared to versican, decorin and lumican also have distinct functions in regulating collagen behaviors. The different ways in which matrix PGs interact with collagen have important implications for understanding the role of the ECM in diseases such as fibrosis and cancer, and suggest that matrix PGs are potential therapeutic targets. [ABSTRACT FROM AUTHOR]

The article reports on CD8+ T lymphocyte response during primary activation or priming. It is said that the activity of CD8+ T cells phases can be governed by instructional programs. It was established in clonal precursors by signals received during priming which is executed by clonal progeny. On the other hand, it has been an important goal for scientist to identify the relevant signals provided during priming.

The article presents the findings of the study which investigates the role of the regulatory T-cells in maintaining intestinal homeostasis. Researchers stated that T-cells interact with 3-phosphoinositide-dependent protein kinase 1 (PDK1) in preventing excessive inflammatory responses. They have also found out that T-cells are activated in response to the commensal microbiota.

The article reports on the study which shows the dynamic interaction of FOXP3, a transcription factor forkhead box 3, with Eos also called Ikzfa, an Ikaros family's zinc finger transcription factor. It notes Eos is needed for the repression of FOXP3-mediated gene in naturally occurring CD4+CD25+ regulatory T cells. It also notes that regulatory T cells have important role for maintaining immune homeostasis.

The article focuses on three studies which examine the role of thymocyte-expressed molecule involved in selection (THEMIS) downstream of T cell receptor in thymocytes. Research groups made use of gene-targeted or ethylnitrosourea (ENU)-induced THEMIS-deficient mice with no obvious abnormalities. All three studies show that the previously unknown T cell specific protein, which they collectively termed as THEMIS, is required for thymocyte positive selection.

The article provides information related to innate immune activation. Clinical application of nonmyeloablative lymphodepletion regimens using total body irradiation (TBI) combined with transfer of tumor-reactive CD8+ T cells is effective in patients with advanced cancer. Studies have suggested two key mechanisms that contribute to the beneficial effect of combining TBI with adoptive cell therapy.

CD1d-dependent NKT cells have been extensively studied; however, the function of CD8+NKT-like cells, which are CD1d-independent T cells with NK markers, remains unknown. Here, we report that CD1d-independent CD8+NKT-like cells, which express both T cell markers (TCRβ and CD3) and NK cell receptors (NK1.1, CD49b and NKG2D), are activated and significantly expanded in mice immunized with GFP-expressing dendritic cells. Distinct from CD1d-dependent NKT cells, CD8+NKT-like cells possess a diverse repertoire of TCRs and secrete high levels of IFN-gamma but not IL-4. CD8+NKT-like cell development is normal in CD1d−/− mice, which suggests that CD8+NKT-like cells undergo a unique development pathway that differs from iNKT cells. Further functional analyses show that CD8+NKT-like cells suppress T-cell responses through elimination of dendritic cells in an antigen-specific manner. Adoptive transfer of antigen-specific CD8+NKT-like cells into RIP-OVA mice prevented subsequent development of diabetes in the animals induced by activated OT-I CD8 T cells. Our study suggests that CD8+NKT-like cells can function as antigen-specific suppressive cells to regulate the immune response through killing antigen-bearing DCs. Antigen-specific down regulation may provide an active and precise method for constraining an excessive immune response and avoiding bypass suppression of necessary immune responses to other antigens. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study which investigates the role of forkhead box P3 (FOXP3)-expressing regulatory T (TReg) cells in promoting antigen-specific B cell and TFH cell. Results showing that regulatory T cells promote antigen-specific B cell responses to influenza virus by influencing the availability of interleukin-2 (IL-2) are explained. Also cited is the mechanism involved in the regulation of the TFH cell response to influenza virus.

The article presents a study which investigates the role of cluster of differentiation 4(CD4) and Thymus (T) cells in the effects of oncogene inactivation. As part of the study, researchers have used a transgenic model of Myc-induced haematopoietic tumorigenesis. Observation was conducted based on the researcher's investigation on the role of the immune system in oncogene addiction. The conclusion of the study is discussed based on the gathered data.

Presents information on research being done by Yasmine Belkaid and colleagues which found out that regulatory T cells can respond specifically to microbial antigens. Explanation that naturally occuring CD4+CD25+ regulatory T cells keep self-reactive T cells but also hamper efficient control of microbial infection; Details on the study conducted by Belkaid and colleagues.

Presents information on a research on orchestrating T cell development, with reference to a study by B. Silva-Santos, D. J. Pennington and A. C. Hayday, published in the December 9, 2004 issue of the journal, "Science."

Deals with the existence of T cells that are odd in nature. Information on T cells that express invariant receptors; Determination of cell types that mediate the selection of such cells.