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Intraepithelial Lymphocytes (intraepithelial + lymphocyte)
Selected AbstractsDuodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009M. M. WALKER Summary Background, Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function. Aim, To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD. Methods, A random sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site. Results, Cases and controls showed similar demographics. Compared to controls, IELs in IBS-constipation were significantly increased (P = 0.005). Mast cells were significantly increased in IBS in D2 (P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 (P < 0.001). Conclusion, Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders. [source] CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2004Anna Ericsson Abstract The integrin CD103 and the chemokine receptor CCR9 are co-expressed on small intestinal CD8+ intraepithelial lymphocytes (IEL), naïve murine CD8+ T cells and by a small population of effector/memory CD8+ T cells, indicating a potential role for CCR9 in regulating CD103 expression and function. Here, we demonstrate that CD103, in contrast to CCR9, is down-regulated on CD8+ T cells following their activation in mesenteric lymph nodes and that effector CD8+ T cells upon initial entry into the small intestinal epithelium are CCR9+CD103,. CD103 was rapidly induced on wild-type CD8+ T cells subsequent to their entry into the small intestinal epithelium, however, CCR9,/, CD8+ T cells exhibited a significant delay in CD103 induction at this site. In addition, the CCR9 ligand, CCL25, that is constitutively expressed in the small intestinal epithelium, induced transient, dose-dependent and pertussis toxin-sensitive CD103-mediated adhesion of CD8+ small intestinal IEL to a murine E-cadherin human Fc (mEFc) fusion protein. Together, these results demonstrate a role for CCR9/CCL25 in promoting the induction and function of CD103 on CD8+ IEL and suggest that this chemokine receptor/chemokine pair may function to regulate lymphocyte-epithelial interactions in the small intestinal mucosa. [source] Distinction between coeliac disease and refractory sprue: a simple immunohistochemical methodHISTOPATHOLOGY, Issue 1 2000N Patey-Mariaud de Serre Aims We recently showed that refractory sprue is distinct from coeliac disease, the former being characterized by abnormal intraepithelial T-lymphocytes expressing a cytoplasmic CD3 chain (CD3c), lacking CD3 and CD8 surface expression, and showing TCR, gene rearrangements. To take advantage of the abnormal phenotype of CD3c + CD8 , intraepithelial lymphocytes (IEL) in refractory sprue we developed a simple method to distinguish coeliac disease from refractory sprue. Methods and results Comparative immunohistochemical studies using anti-CD3 and anti-CD8 antibodies were applied on paraffin-embedded and frozen biopsy specimens in refractory sprue (n = 6), coeliac disease (n = 10), healthy controls (n = 5) and suspected refractory sprue (n = 6). Comparable results were obtained on fixed and frozen biopsy specimens. In four of the six patients with suspected refractory sprue, abnormal CD3c + CD8 , IEL and TCR, gene rearrangements were found, as in refractory sprue; the remaining two patients had normal (CD3 + CD8 +) IEL and no TCR, gene rearrangements. Both patients had coeliac disease, as one failed to comply with a gluten-free diet, while the other was a slow responder. Conclusion This simplified immunostaining method using anti-CD3 and anti-CD8 antibodies on paraffin sections can distinguish active coeliac disease from refractory sprue and should prove useful in clinical practice. [source] T cells developing in fetal thymus of T-cell receptor ,-chain transgenic mice colonize ,, T-cell-specific epithelial niches but lack long-term reconstituting potentialIMMUNOLOGY, Issue 1 2006Karin Leandersson Summary The ,, T cells generated during mouse fetal development are absolutely dependent on their invariant T-cell receptors (TCRs) for their function. However, there is little information on whether the epithelial homing properties of fetal T cells might also be developmentally induced by factors unrelated to TCR specificity. We have previously described TCR ,-chain transgenic (2B4 TCR-, TG) mice, in which the transgenic TCR ,-chain is expressed early, already at embryonic day 14 (E14). These mice have a large population of ,,, T-cell-like' CD4, CD8, (double-negative; DN) ,, T cells, some of which develop during E14,E18 contemporarily to intraepithelial lymphocytes (IELs) expressing invariant TCR-,,. Using the 2B4 TCR-, TG mouse model we have been able to more precisely study the impact of a variant TCR expression on IEL development and homing. In this study we show that TCR-, TG and TCR-, TG crossed to TCR-,-deficient mice (TCR-, TG × TCR-,,/,) carry TG TCR-,+ dendritic epidermal T cells (DETCs) and TCR-, TG+ IELs in the small intestine. The TG+ DETCs develop and seed the epidermis with similar kinetics as V,5+ DETCs of normal mice, in contrast to the TCR-,,+ DETCs found in TCR-,,/, mice. However, whereas the intestinal TCR-, TG+ IELs persist in old mice (> 20 months), the TCR-, TG+ DETCs do not. The data in this study indicate that the timing of TCR expression and thereby development during ontogeny regulates the specific homing potential for fetal T cells but not their subsequent functions and properties. [source] Oats in the treatment of childhood coeliac disease: a 2-year controlled trial and a long-term clinical follow-up studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006K. HOLM Summary Background The exclusion of oats from the diet in coeliac disease is controversial. Aim To study the long-term safety of oats in the treatment of children with coeliac disease. Methods Altogether 32 children with coeliac disease were enrolled in a 2-year controlled trial. Twenty-three children in remission were randomized either to oats or gluten challenge; when small bowel histological relapse was evident after gluten challenge, a gluten-free diet including oats was started. Furthermore, nine newly detected coeliac patients adopted an oat-containing gluten-free diet. Small bowel mucosal morphology, CD3+, ,,+ and ,,+ intraepithelial lymphocytes, human leucocyte antigen (HLA) DR expression and coeliac serology were determined. After the trial, the children were allowed to eat oats freely; follow-up was extended up to 7 years. Results In coeliac children in remission, oats had no detrimental effect on intestinal histology or serology during the 2-year trial. In contrast, the gluten-challenge group relapsed after 3,12 months. Complete recovery from the disease was accomplished in all relapsed and newly detected patients on an oat-containing gluten-free diet. After the trial, 86% of the children preferred to consume oats and they all remained in remission. Conclusion In most children with coeliac disease, long-term consumption of oats is well tolerated, and it does not result in small bowel mucosal deterioration or immune activation. [source] T cell-mediated immunoregulation in the gastrointestinal tractALLERGY, Issue 4 2009L. Saurer In the intestinal tract, only a single layer of epithelial cells separates innate and adaptive immune effector cells from a vast amount of antigens. Here, the immune system faces a considerable challenge in tolerating commensal flora and dietary antigens while preventing the dissemination of potential pathogens. Failure to tightly control immune reactions may result in detrimental inflammation. In this respect, ,conventional' regulatory CD4+ T cells, including naturally occurring and adaptive CD4+ CD25+ Foxp3+ T cells, Th3 and Tr1 cells, have recently been the focus of considerable attention. However, regulatory mechanisms in the intestinal mucosa are highly complex, including adaptations of nonhaematopoietic cells and innate immune cells as well as the presence of unconventional T cells with regulatory properties such as resident TCR,, or TCR,, CD8+ intraepithelial lymphocytes. This review aims to summarize the currently available knowledge on conventional and unconventional regulatory T cell subsets (Tregs), with special emphasis on clinical data and the potential role or malfunctioning of Tregs in four major human gastrointestinal diseases, i.e. inflammatory bowel diseases, coeliac disease, food allergy and colorectal cancer. We conclude that the clinical data confirms some but not all of the findings derived from experimental animal models. [source] Host cell-mediated responses to infection with CryptosporidiumPARASITE IMMUNOLOGY, Issue 12 2000V. McDonald The coccidian Cryptosporidium infects epithelial cells of a variety of vertebrate hosts and is the causative agent of cryptosporidiosis. In mammals, including humans and domestic animals, C. parvum infects the gastrointestinal tract producing an acute watery diarrhoea and weight loss. CD4+ T-cell-deficient hosts have increased susceptibility to infection with the parasite and may develop severe life-threatening complications. The host responses which induce protective immunity and contribute to pathogenesis are poorly understood. In the immunological control of infection, recent studies with murine infection models suggest that IFN-, plays a key role in a partially protective innate immunity against infection identified in immunocompromised mice and also in the elimination of infection mediated by CD4+ T-cells. At the mucosal level, CD4+ intraepithelial lymphocytes are involved in the control of cryptosporidial infection, acting at least in part through production of IFN-, which has a direct inhibitory effect on parasite development in enterocytes. Primary infection of ruminants induces an intestinal inflammatory response in which increased numbers of various T-cell subpopulations appear in the villi. In addition, infection results in increased intestinal expression of pro-inflammatory cytokines such as IL-12, IFN-, and TNF-,. Because these cytokines appear to be important in the aetiology of inflammatory bowel disease, it is possible that they are involved in the mucosal pathogenesis of cryptosporidiosis. [source] Bone marrow stem cells do not repopulate the healthy upper respiratory tract,PEDIATRIC PULMONOLOGY, Issue 4 2002Jane C. Davies MD Abstract Recent studies reported differentiation of both bone marrow and tissue-specific stem cells into cells of other organs. The demonstration that bone marrow stem cells differentiate into human hepatocytes in vivo has raised the possibility of new therapeutic approaches for liver disease. For diseases such as cystic fibrosis (CF), correction of the respiratory epithelium is being attempted by gene therapy. Differentiation of bone marrow stem cells into epithelium of the lung and airway was recently reported in an animal model, and would provide an alternative approach. We examined the nasal epithelium of female patients up to 15 years after gender-mismatched bone marrow transplantation. Donor-derived epithelial cells were sought with a combination of Y-chromosome fluorescence in situ hybridization and anti-cytokeratin antibody. In nasal brushing samples from 6 transplant-recipients, a median of 2.5% (range, 0.7,18.1%) of nuclei was male and identified as being of donor-origin. However, a complete absence of staining with anti-cytokeratin antibodies confirmed that these were not epithelial cells, but were likely to be either intraepithelial lymphocytes or mesenchymal cells. Following whole bone marrow transplantation, bone marrow progenitor cells do not differentiate into respiratory epithelium of the healthy upper airway. The differences between this and other studies could relate to the cells transplanted, to differential rates of turnover, or to the requirement for specific triggers to stimulate migration and differentiation. In the absence of such conditions, whole bone marrow transplantation is unlikely to provide a route for correction of the CF airway. Pediatr Pulmonol. 2002; 34:251,256. © 2002 Wiley-Liss, Inc. [source] The Influence of Pre- and Post-ovulatory Insemination and Early Pregnancy on the Infiltration by Cells of the Immune System in the Sow OviductREPRODUCTION IN DOMESTIC ANIMALS, Issue 5 2006J Jiwakanon Contents The aim of this study was to investigate the influence of pre- and post-ovulatory insemination and early pregnancy on the distribution of immune cells in the oviduct. Eighteen sows were pre-ovulatory and sixteen sows were post-ovulatory inseminated and slaughtered at different times, 5,6 h after insemination, 20,25 h and approximately 70 h after ovulation, day 11 and day 19. Immediately after slaughter, oviductal samples of three different segments (isthmus, ampulla and infundibulum) were fixed, embedded in plastic resin and stained with toluidine blue or cryofixed and stored in a freezer at ,70°C until analysed by immunohistochemistry (pre-ovulatory inseminated sows) with an avidin,biotin peroxidase method. Quantitative and qualitative examinations of oviductal epithelium and subepithelial connective tissue were performed by light microscopy. After pre- or post-ovulatory insemination, neutrophils were not observed in the oviductal epithelium from any of the segments or groups. The numbers of intraepithelial lymphocytes of all sows as well as CD2- and CD3-positive cells of the pre-ovulatory inseminated sows were higher in the infundibulum than in the other segments (p , 0.001). In the subepithelial connective tissue of the pre-ovulatory inseminated sows, significantly higher numbers of lymphocytes (p , 0.001) and plasma cells (p , 0.001) were found in infundibulum than in isthmus. Neutrophils were found mainly in infundibulum, the number approximately 40 h after pre-ovulatory insemination was significantly higher (p , 0.05) than in the other groups and segments. Significantly higher numbers of CD2 than CD3-positive cells were found for all groups and segments. In the subepithelial connective tissue of post-ovulatory inseminated sows, the numbers of lymphocytes was higher (p , 0.001) at day 19 than up to 50 h after insemination and lower (p , 0.001) in isthmus than in ampulla and infundibulum. Neutrophils were found in infundibulum in almost all groups and the number was significantly higher (p , 0.05) in the infundibulum up to 50 h after insemination than in other segments. In the oviductal epithelium, no influence of insemination was found on the presence of phagocytes, i.e. neutrophils and macrophages, but on lymphocytes. In the infundibular connective tissue, pre-ovulatory insemination had an effect on neutrophil distribution, indicating an active immune response to insemination in the upper segment. Post-ovulatory insemination changed the oviductal immune cell pattern. [source] Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa,APMIS, Issue 6 2005Review article Intestinal intraepithelial lymphocytes (IELs) belong to a unique T-cell population interspersed between epithelial cells of both the small and large intestine. It is becoming increasingly recognised that an increased number of IELs with a normal villous architecture is within the wide spectrum of histological abnormalities observed in coeliac disease. An increased number of IELs is the earliest pathological change following gluten challenge and a high IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be reported in routine small bowel biopsies. However, it is evident that not all small intestinal biopsy specimens showing increased IELs are explained by gluten sensitivity. Increased IELs in small bowel mucosa have also been associated with autoimmune disorders, tropical sprue, food protein intolerance, Helicobacter pylori -associated gastritis, peptic duodenitis, parasitic and viral infections, as well as the development of intestinal lymphoma. Histological examination of a biopsy specimen of the small bowel remains the diagnostic gold standard for coeliac disease. There will be an ever increasing demand for histological confirmation of gluten sensitivity in patients in whom the classic microscopic appearance of flattened villi may not have fully developed. The more widespread recognition by histopathologists of the pattern of injury manifested by increased numbers of IELs in intestinal biopsy specimens will certainly help in early diagnosis of coeliac disease, lessen diagnostic confusion and influence the modern practice of gastrointestinal tract medicine. This review discusses some of the recent developments in clinical pathology pertaining to increased IELs in small bowel mucosal biopsies. [source] Thymus-leukemia antigen (TL) as a major histocompatibility complex (MHC) class Ib molecule and tumor-specific antigenCANCER SCIENCE, Issue 6 2004Kunio Tsujimura Mouse thymus-leukemia antigens (TL) belong to the family of major histocompatibility complex (MHC) class Ib antigens and have a unique mode of expression, i.e., in contrast to other MHC class Ib or la antigens, they are found restricted to the intestines in all mouse strains, but also in the thymus of certain strains (TL+ strains). Nevertheless, a proportion of T lymphomas/leukemias in strains that do not express TL in the thymus (TL, strains) feature TL as a tumor antigen. TL was originally defined serologically, but subsequently we have succeeded in generating T cell receptor (TCR) ,, and ,, cytotoxic T lymphocytes (CTL) recognizing TL. By use of TL tetramers free from peptides and transfectants expressing various TL/H-2 chimeric molecules, we have been able to show that TL-specific CTL recognize the ,1 /,2 domain of TL without any additional antigen molecules. We previously reported that one of TL's functions in the thymus is positive selection of TCR,, CTL. Recent studies with TL tetramers revealed that they can bind to normal intestinal intraepithelial lymphocytes (ilEL) and thymocytes in a CD8-dependent, but TCR/CD3-independent manner, while their binding to TL-specific CTL is TCR/CD3-and CDS-dependent. The possible significance of these findings in relation to the roles of TL in the intestines is discussed. We have long been interested in TL as a model tumor antigen which shares characteristics with human differentiation tumor antigens, and we have demonstrated that growth of TL+ lymphoma cells in vivo is suppressed by immunization with TL+ skin or dendritic cells (DC) from TL transgenic mice. In addition, anti-tumor effects against TL+ T lymphomas were obtained by adoptive transfer of TL tetramer strongly-positive TL-specific CTLs. [source] Proteins specifically hyperexpressed in a coeliac disease patient with aberrant T cellsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2007V. De Re Summary An aberrant T cell population is the basis for diagnosis of refractory coeliac disease and determines the risk of enteropathy-associated T cell lymphoma. This disease is serious with a poor survival. Pathogenetic mechanisms sustaining aberrant T cell proliferation remain unknown. Recently, alemtuzumab has been proposed as a promising new approach to treat these patients. Only few single cases have been tested at present; nevertheless, in all the cases a clinical improvement was observed. However, whether intraepithelial lymphocytes have been targeted effectively by alemtuzumab is still debated. This study reports, using two-dimensional difference gel electrophoresis (2D DIGE), hyperexpressed proteins associated specifically with aberrant T cells found in a patient with coeliac disease by comparison of the protein expression of this sample with that of patients with coeliac disease and polyclonal T cells or with control subjects. The data demonstrated a significantly higher expression of IgM, apolipoprotein C-III and Charcot,Leyden crystal proteins in a duodenal biopsy specimen of the patient with clonal T cells compared with that of other patients. These preliminary results allow hypothesizing different clinical effects of alemtuzumab in patients with coeliac disease and aberrant T cell proliferation, because as well as the probable effect on T cells, alemtuzumab could exert its effect by acting on inflammatory associated CD52+ IgM+ B cells and eosinophil cells, known to produce IgM and Charcot,Leyden crystal proteins, that we demonstrated to be altered in this patient. The results also emphasize the possible association of apolipoprotein with aberrant T cell proliferation. [source] Using radioligand-binding assays to measure tissue transglutaminase autoantibodies in young childrenACTA PAEDIATRICA, Issue 8 2004D Agardh Aim: To measure autoantibodies against tissue transglutaminase (tTG) in young children prospectively screened for coeliac disease (CD). Methods: In total, 652 children aged 2.9 (2.5,4.2) y were analysed for IgA-tTG and IgG-tTG with radioligand-binding assays and IgA endomysial antibodies (EMA) by indirect immunofluorescence. Antibody-positive children were retested after 1.2 (range 0.2,1.9) y. Intestinal biopsy was performed on children with persistently high antibody levels. Results: In total, 3.2% (95% CI: 1.9,4.6%) of the 652 children were positive for at least one antibody at baseline: 2.5% (95% CI: 1.3,3.7%) for IgA-tTG, 1.7% (95% CI: 0.7,2.7%) for IgG-tTG and 2.9% (95% CI: 1.6,4.2%) for IgA-EMA, respectively. Ten children were positive for all three antibodies, five for both IgA-tTG and EMA, four for EMA only, one for IgA-tTG and another for IgG-tTG. IgA-EMA titres correlated with IgA-tTG levels (r= 0.73, p= 0.0003). At follow-up, seven of 20 children remained positive for all three antibodies, three for IgA-tTG only, one for both IgA-tTG and EMA, one for IgA-tTG and IgG-tTG, and the remaining child refused further participation. Three biopsies showed villous atrophy, two increased intraepithelial lymphocytes and two normal findings. Biopsy was not performed in four children with low or declining tTG antibody levels at follow-up and in one child who declined. CD was evident in 0.5% (95% CI: 0.0,1.0%) (3/652). Conclusion: This study revealed a high number of young children positive for tTG antibodies as well as EMA, but the majority showed declining levels in both antibodies over time. We suggest using radioligand-binding assays for quantitative measurement of tTG antibodies when change in antibody levels is studied in young children. [source] | ||||||||||