Intestinal epithelial barrier and mucosal immunity

Intestinal mucosa integrates primary digestive functions with immune functions such as pathogen surveillance, antigen transport and induction of mucosal immunity and tolerance. Intestinal adaptive immunity is elicited in organized mucosa-associated lymphoid tissue (O-MALT) that is composed of antigen-presenting cells and lymphocytes and achieved by effector cells widely distributed in mucosa (diffuse MALT or D-MALT). Interaction between the intestinal epithelium, the O-MALT and the diffuse MALT plays a critical role in establishing an adequate immune response. In regions associated to O-MALT, lympho-epithelial cross-talks lead to acquisition of a specific epithelial phenotype that contributes to O-MALT organization and functionality. Beyond the expression of several innate immune functions, the intestinal epithelium may directly take up and present antigens due to the expression of major histocompatibility complex (MHC) and MHC-related molecules. A complex genetic program that will be outlined in the present review controls the development of immune functions of the intestinal epithelium. The effect of environmental signals on the modulation of this ontogenetic program during development and neonatal life, from bioactive components of amniotic fluid to lactation and bacterial colonization, will be discussed.     

The battle against immunopathology: infectious tolerance mediated by regulatory T cells

Infectious tolerance is a process whereby one regulatory lymphoid population confers suppressive capacity on another. Diverse immune responses are induced following infection or inflammatory insult that can protect the host, or potentially cause damage if not properly controlled. Thus, the process of infectious tolerance may be critical in vivo for exerting effective immune control and maintaining immune homeostasis by generating specialized regulatory sub-populations with distinct mechanistic capabilities. Foxp3(+) regulatory T cells (T(regs)) are a central mediator of infectious tolerance through their ability to convert conventional T cells into induced regulatory T cells (iT(regs)) directly by secretion of the suppressive cytokines TGF-β, IL-10, or IL-35, or indirectly via dendritic cells. In this review, we will discuss the mechanisms and cell populations that mediate and contribute to infectious tolerance, with a focus on the intestinal environment, where tolerance induction to foreign material is critical.     

The functions of mucosal T cells in containing the indigenous commensal flora of the intestine

There is an immense load of non-pathogenic commensal bacteria in the distal small intestine and the colon of mammals. The physical barrier that prevents penetration (translocation) of these organisms into the body is a simple epithelium comprised of the single enterocyte/colonocyte cell layer with its overlying mucus. In this review, we discuss the roles of intestinal T cells in initiating and regulating innate and adaptive mucosal immune responses of the mucosal immune system that avoid or limit penetration of the commensal intestinal bacteria. Received 9 August 2002; accepted 9 September 2002 RID="*" ID="*"Corresponding author.     

Differential interaction of 2,4,6-trinitrobenzenesulfonic (TNBS) and 2,4-dinitrobenzenesulfonic (DNBS) acids on mouse lymphocytes]

Modifications of lymphoid cells with dinitro-2,4 phenylsulfonic acid (DNBS) or trinitro-2,4,6 phenylsulfonic acid (TNBS) have been studied. TNBS action always produces an electrophoretic mobility increase in relation with the amount of amino-groups, according to the cell type. DNBS action produces an electrophoretic mobility increase for B cells of spleen and a decrease for T cells of spleen and thymic cells. The hydrophobic fluorescent probe 1-anilino-8-naphthalene sulphonate used to study conformational changes of cells revealed a slight fluorescence decrease for TNP-modified cells and an important fluorescence increase for DNP-modified cells.     

Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity

It is now well demonstrated that the repertoire of T cells includes not only cells that recognize specific MHC-presented peptide antigens, but also cells that recognize specific self and foreign lipid antigens. This T cell recognition of lipid antigens is mediated by a family of conserved MHC class I-like cell surface glycoproteins known as CD1 molecules. These are specialized antigen-presenting molecules that directly bind a wide variety of lipids and present them for T cell recognition at the surface of antigen-presenting cells. Distinct populations of T cells exist that recognize CD1-presented lipids of microbial, environmental or self origin, and these T cells participate in immune responses associated with infectious, neoplastic, autoimmune and allergic diseases. Here we review the current knowledge of the biology of the CD1 system, including the structure, biosynthesis and trafficking of CD1 molecules, the structures of defined lipid antigens and the types of functional responses mediated by T cells specific for CD1-presented lipids.     

Nephrin in human lymphoid tissues

When nephrin, the protein product of NPHS1, was cloned, it was proposed to be specific for the kidney glomerular podocytes. Recently, however, new reports have emerged verifying additional nephrin expression sites, particularly the insulin-producing β cells of the pancreas, as well as the central nervous system. In this study, we demonstrate nephrin expression in lymphoid tissues, specifically the tonsil, adenoid and lymph node. Nephrin mRNA expression levels were 4-fold higher in tonsils and adenoids than in thymus or B lymphocytes, and 20-fold higher than in T lymphocytes or monocytes, as shown by quantitative RT-PCR analysis. Anti-nephrin antibodies recognised a specific 165-kDa band in lysates of tonsil and adenoid. In immunofluorescence and immunohistochemichal stainings of adenoid and lymph node sections, nephrin-positive cells were detected in the germinal centres of the lymphoid follicles in a staining pattern typical for interdigitating cells. These results indicate a definite and additional presence of nephrin in lymphoid tissue. Received 17 October 2005; received after revision 22 November 2005; accepted 20 December 2005     

Serotonin-containing cells in the ascidian endostyle

Summary In the ascidian endostyle, all fluorescence due to serotonin is localized in the peripheral, iodine-binding area of the endostylar epithelium, which is homologous to the vertebrate thyroid. The amine appears to be stored in granule-containing cells which may correspond to the vertebrate calcitocytes.We are grateful to Dr M.P. Gorbunova for helpful advise and diseussion.     

Molecular recognition of microbial lipid-based antigens by T cells

The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells leading to antigen-specific activation. Over the past decades, numerous CD1-presented self- and bacterial lipid-based antigens have been isolated and characterized. However, our understanding at the molecular level of T cell immunity to CD1 molecules presenting microbial lipid-based antigens is still largely unexplored. Here, we review the insights and the molecular basis underpinning the recognition of microbial lipid-based antigens by T cells.     

Activation of cytotoxic T cells by solid tumours?

Tumour-specific cytotoxic T cells (CTLs) are among the best-defined biological anticancer weapons. Nevertheless, they often fail to control tumour growth in vivo. Many reasons for this have been evoked tumours may actively inhibit CTLs, or may protect them selves from CTL recognition by various means. However, one does not necessarily need to postulate such active immune evasion mechanisms specifically acquired by tumour cells. In this review we argue that the failure of immune protection is due to the intrinsic inability of tumours to activate an effective immune response, and that many tumours are similar to normal issues in this respect. It is striking to see that the majority of the so-called immune escape mechanisms are not specifically acquired by selected tumour cells, but are common mechanisms shared between solid tumours and normal, healthy tissues. Immune responses are poor because tumour antigens do not efficiently localize to lymph follicles in lymphoid tissues, and are not efficiently presented to CTLs in an immunogenic context. The fact that tumours do not induce CTLs but are often susceptible to lymphocyte-mediated cytotoxicity indicates that more intensified immunization protocols should result in improved clinical outcome.     

The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation

A challenging task for the adaptive immune system of vertebrates is to identify and eliminate intracellular antigens. Therefore a highly specialized antigen presentation machinery has evolved to display fragments of newly synthesized proteins to effector cells of the immune system at the cell surface. After proteasomal degradation of unwanted proteins or defective ribosome products, resulting peptides are translocated into the endoplasmic reticulum by the transporter associated with antigen processing and loaded onto major histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are transported via the secretory pathway to the cell surface where they are then inspected by cytotoxic T lymphocytes, which can trigger an immune response. This review summarizes the current view of the intracellular machinery of antigen processing and of viral immune escape mechanisms to circumvent destruction by the host. Received 4 October 2005; received after revision 19 November 2005; accepted 24 November 2005     

Immunity and cancer: suppressor effect on the cytotoxic activity of lymphoid cells from animals carrying syngeneic tumors]

When it is tested in vitro, the cytotoxic action of lymphocytes from mice bearing a syngeneic tumour (T2) vary with the age of the graft. At a time when it is very low, the lymphoid cells are cultivated for 3 days and then can be fractionated in two subpopulations on a glass bead column: a cytotoxic "non adherent" group of cells and an "adherent" group that inhibits the activity of the first group when it is added to it.     

The multifaceted Paneth cell

Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs. Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation. Received 6 June 2001; received after revision 26 July 2001; accepted 27 July 2001     

Intestinal epithelial barrier and mucosal immunity

The mucosal immune system acts as a first line of defense against bacterial and viral infections while also playing a crucial role in the establishment and maintenance of mucosal homeostasis between the host and the outside environment. In addition to epithelial cells and antigen-presenting cells (dendritic cells and macrophages), B and T lymphocytes form a dynamic mucosal network for the induction and regulation of secretory IgA (S-IgA) and cytotoxic T lymphocyte (CTL) responses. This review seeks to shed light on the pathways of induction and regulation of these responses and to elucidate the role they simultaneously play in fending off pathogen invasion and maintaining mucosal homeostasis.     

Effects of Freund's complete adjuvant on the dirunal rhythms of neuroendocrine processes and ornithine decarboxylase activity in various tissues of male rats

The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.     

Gamma-glutamyl-transpeptidase in lymphatic tissues of Mastomys natalensis during an infection with Acanthocheilonema viteae

During Acanthocheilonema viteae infection, the specific activity of gamma-glutamyltranspeptidase (gamma-GT) increased in peritoneal exudate cells and bone marrow and decreased in lymph nodes of Mastomys natalensis throughout the course of infection. However, though there was an increase in specific activity of gamma-GT in thymus and spleen during the prepatent phase of A. viteae infection, the level either returned to normal or decreased during the latent phase of infection. A close correlation was observed between the host's immune status during A. viteae infection and the level of gamma-GT in lymphoid tissues.     

The unique features of follicular T cell subsets

The germinal center (GC) reaction is critical for humoral immunity, but also contributes adversely to a variety of autoimmune diseases. While the major protective function of GCs is mediated by plasma cells and memory B cells, follicular helper T (TFH) cells represent a specialized T cell subset that provides essential help to the antigen-specific B cells in the form of membrane-bound ligands and secreted factors such as IL-21. Recent studies have revealed that TFH cells are capable of considerable functional diversity as well as possessing the ability to form memory cells. The molecular basis of this plasticity and heterogeneity is only now emerging. It has also become apparent that several other populations of follicular T cells exist, including natural killer T cells and regulatory T cells. In this review we will discuss the function of follicular T cells and interaction of these populations within the GC response.     

Intestinal epithelial barrier and mucosal immunity

Both innate immunity and mucosal surfaces provide the first line of defence against mucosal infections. Innate immunity is a universal and evolutionarily conserved form of host defence that senses microbial organisms. Recent advances in the field of immunology are due mainly to the discovery of the role of Toll-like receptors (TLRs), which recognize conserved microbial molecules. TLR stimulation induces specific patterns of gene expression that lead to the shaping of innate and adaptive immunity. Since mucosal tissues are colonized by innocuous microflora and challenged by infectious pathogens, activation of TLRs in epithelial and lamina propria cells must be tightly controlled to avoid inappropriate signalling that might lead to mucosal inflammation. This review aims to highlight novel insight on the molecules, pathways and gene expression networks associated with microbial recognition by TLRs and mucosal immunity.     

Alterations in bone-marrow cellularity following thymectomy in rats.

The number of nucleated marrow cells was decreased following neonatal thymectomy in rats, and was corrected by administration of syngeneic lymphoid cells, or by implantation of a syngeneic testis. These results suggest that, in the rat, as has been shown previously in the mouse, lymphoid cells exert parital control over bone marrow cellularity and this effect may be further modulated by sex steroids.