Role In Mucosal Immunity Research Articles

Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (IEL) constitute the first lymphoid compartment to encounter dietary antigens and intestinal pathogens. IEL are proposed to be involved in the defence against bacterial and viral invasion and to play an important role in mucosal immunity. Fas (CD95/APO-1) is a surface receptor that induces apoptotic cell death upon ligation with Fas ligand (FasL). The aim of this study was to examine the expression and function of Fas and FasL on freshly isolated normal human colonic IEL. The expression and function of Fas and FasL on IEL isolated from 40 normal colonic specimens were examined by flow cytometry, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and DNA-release cytotoxicity assay. Virtually all CD3+ IEL (95.2 +/- 4.3%) expressed Fas and were sensitive to agonistic anti-Fas antibody, whereas only 56.6 +/- 8.4% of peripheral T lymphocytes expressed Fas and were resistant to the antibody. We also detected FasL mRNA and protein (40.1 +/- 4.2%) on IEL, and found that IEL exerted FasL-mediated cytotoxicity against Fas-expressing target cells. These findings suggest that human IEL are activated in situ but are tightly regulated by the constitutive expression of functional Fas and FasL to maintain homeostasis of the mucosal immune system.

Origins and functions of B-1 cells with notes on the role of CD5.

Whether B-1a (CD5+) cells are a distinct lineage derived from committed fetal/neonatal precursors or arise from follicular B-2 cells in response to BCR ligation and other, unknown signals remains controversial. Recent evidence indicates that B-1a cells can derive from adult precursors expressing an appropriate specificity when the (self-) antigen is present. Antibody specificity determines whether a B cell expressing immunoglobulin transgenes has a B-2, B-1a or marginal zone (MZ) phenotype. MZ cells share many phenotypic characteristics of B-1 cells and, like them, appear to develop in response to T independent type 2 antigens. Because fetal-derived B cell progenitors fail to express terminal deoxynucleotidyl transferase (TdT) and for other reasons, they are likely to express a repertoire that allows selection into the B-1a population. As it is selected by self-antigen, the B-1 repertoire tends to be autoreactive. This potentially dangerous repertoire is also useful, as B-1 cells are essential for resistance to several pathogens and they play an important role in mucosal immunity. The CD5 molecule can function as a negative regulator of BCR signaling that may help prevent inappropriate activation of autoreactive B-1a cells.

Exercise effects on mucosal immunity

The present review examines the effects of exercise on mucosal immunity in recreational and elite athletes and the role of mucosal immunity in respiratory illness. Habitual exercise at an intense level can cause suppression of mucosal immune parameters, while moderate exercise may have positive effects. Saliva is the most commonly used secretion for measurement of secretory antibodies in the assessment of mucosal immune status. Salivary IgA and IgM concentrations decline immediately after a bout of intense exercise, but usually recover within 24 h. Training at an intense level over many years can result in a chronic suppression of salivary immunoglobulin levels. The degree of immune suppression and the recovery rates after exercise are associated with the intensity of exercise and the duration or volume of the training. Low levels of salivary IgM and IgA, particularly the IgA1 subclass, are associated with an increased risk of respiratory illness in athletes. Monitoring mucosal immune parameters during critical periods of training provides an assessment of the upper respiratory tract illness risk status of an individual athlete. The mechanisms underlying the mucosal immune suppression are unknown.

The Polymeric Immunoglobulin Receptor Translocates Pneumococci across Human Nasopharyngeal Epithelial Cells

The polymeric immunoglobulin receptor (pIgR) plays a crucial role in mucosal immunity against microbial infection by transporting polymeric immunoglobulins (pIg) across the mucosal epithelium. We report here that the human pIgR (hpIgR) can bind to a major pneumococcal adhesin, CbpA. Expression of hpIgR in human nasopharyngeal cells and MDCK cells greatly enhanced pneumococcal adherence and invasion. The hpIgR-mediated bacterial adherence and invasion were abolished by either insertional knockout of cbpA or antibodies against either hpIgR or CbpA. In contrast, rabbit pIgR (rpIgR) did not bind to CbpA and its expression in MDCK cells did not enhance pneumococcal adherence and invasion. These results suggest that pneumococci are a novel example of a pathogen co-opting the pIg transcytosis machinery to promote translocation across a mucosal barrier.

Ileal and jejunal Peyer's patches play distinct roles in mucosal immunity of sheep.

The majority of pathogens enter the body through mucosal surfaces and it is now evident that mucosal immunity can provide effective disease protection. However, the induction of mucosal immunity will require efficient targeting of mucosal vaccines to appropriate mucosa-associated lymphoid tissue. An animal model, based upon the surgical preparation of sterile intestinal 'loops' (blind-ended segments of intestine), was developed to evaluate mucosal and systemic immune responses to enteric vaccines in ruminants. The effectiveness of end-to-end intestinal anastomoses was evaluated and fetal surgery did not disrupt normal intestinal function in lambs up to 6-7 months after birth. The immunological competence of Peyer's patches (PP) within the intestinal 'loops' was evaluated with a human adenovirus 5 vector expressing the gD gene of bovine herpesvirus-1. This vaccine vector induced both mucosal and systemic immune responses when injected into intestinal 'loops' of 5-6-week-old lambs. Antibodies to the gD protein were detected in the lumen of intestinal 'loops' and serum and PP lymphocytes proliferated in response to gD protein. The immune competence of ileal and jejunal PP was compared and these analyses confirmed that jejunal PP are an efficient site for the induction of mucosal immune responses. This was confirmed by the presence of gD-specific antibody-secreting cells in jejunal but not ileal PP. Systemic but not mucosal immune responses were detected when the vaccine vector was delivered to the ileal PP. In conclusion, this model provided an effective means to evaluate the immunogenicity of potential oral vaccines and to assess the immunological competence of ileal and jejunal Peyer's patches.

A role for mucosal immunity in resistance to HIV infection

In a recent, thought-provoking novel by Elizabeth McCracken (The Giant's House. Avon Books, New York, 1997), two characters discuss love and its impossibilities. One brashly claims to be “immune to love”, explaining the concept to his perplexed interlocutor, “…people become immune to love like they become immune to any disease. Either they had it bad early in life, like chicken pox and that's that; or they keep getting exposed to it in little doses and build up an immunity; or somehow they just don't catch it, something in’em is born resistant. I'm the last type. I'm immune to love and poison ivy”. (p. 275) (E. McCracken, The Giant's House. Avon Books, New York, 1997). Substitute the words ‘HIV infection’ for ‘love’ and this intriguing metaphor summarizes the state of the art working hypotheses for the phenomenon of resistance to HIV infection in HIV-exposed individuals who, against all odds, do not seroconvert. These hypotheses will be discussed hereafter and particular emphasis will be placed upon a possible role for mucosal immunity in this phenomenon.

Different regulatory pathways employed in cytokine-enhanced expression of secretory component and epithelial HLA class I genes.

The transmembrane secretory component (SC, or pIg receptor) plays a crucial role in mucosal immunity by translocating dimeric IgA and pentameric IgM through exocrine epithelia. This receptor is up-regulated by cytokines in parallel with increased epithelial HLA expression. By use of the human epithelial cell line HT-29m3, we show that IFN-gamma, TNF-alpha and IL-4 activate transcription of the SC gene. This activation was slow, suggesting mediation via newly synthesized protein factors. IFN-gamma and TNF-alpha, but not IL-4, also up-regulated expression of HLA class I genes. However, this gene induction was rapid and did not depend on new protein synthesis. Nuclear run-on experiments showed that the transcription rate of HLA class I genes nearly peaked after only 30 min of IFN-gamma or TNF-alpha stimulation, whereas the SC transcription rate did not peak until after 20-36 h of IFN-gamma, TNF-alpha or IL-4 stimulation. Gel electrophoresis mobility shift assays demonstrated binding of nuclear proteins from cytokine-stimulated HT-29 cells to consensus elements in the promoter of the SC gene, involving the binding site for the nuclear factor-kappaB p50 subunit after TNF-alpha stimulation, and IFN-stimulated response element after IFN-gamma stimulation (and weakly after TNF-alpha. Our observations in vitro likely parallel events in vivo by which activated mucosal T cells and macrophages enhance pIg receptor-mediated external transport of secretory IgA and IgM and up-regulate epithelial HLA expression.

Increased CD1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis.

Cluster of differentiation 1 (CD1) is a family of four distinct nonpolymorphic major histocompatibility complex class I-like molecules that can present microbial nonpeptide lipid antigens to T cells. Among the CD1 gene family, CD1d is found in a wide range of tissues including the intestine and liver, and has been proposed to play an important role in mucosal immunity. Primary biliary cirrhosis (PBC) is an immune-mediated liver disease involving the intrahepatic small bile ducts, which also belong to the mucosal immune system. In this study, we studied the expression of CD1d in patients with PBC and compared the data with those of patients with hepatic sarcoidosis, primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), and normal liver as controls. CD1d was found to be expressed in hepatocytes in all cases examined, and in epithelioid granuloma cells in 19 of 22 PBC livers and in 4 of 4 livers with hepatic sarcoidosis. In addition, CD1d was focally expressed on epithelial cells of the small bile ducts in approximately 50% of the PBC patients but in no controls. Such bile duct epithelial staining of CD1d was seen in early-stage PBC and virtually absent in late-stage PBC. Moreover, there was no evidence of expression of CD1d in large bile duct epithelial cells of PBC. The CD1d on biliary epithelial cells in PBC may be involved in the antigen presentation of microbial lipid antigen(s) to surrounding T cells. Alternatively, modified endogenous lipidic compounds may share analogy with bacterial lipid antigens and explain CD1d expression, a possible epiphenomenon rather than a proof of bacterial involvement.

Intestinal intraepithelial lymphocytes are primed for gamma interferon and MIP-1beta expression and display antiviral cytotoxic activity despite severe CD4(+) T-cell depletion in primary simian immunodeficiency virus infection.

Intraepithelial lymphocytes (IEL) are a critical effector component of the gut-associated lymphoid tissue (GALT) and play an important role in mucosal immunity as well as in the maintenance of the epithelial cell integrity and barrier function. The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of rhesus macaques would cause alterations in the immunophenotypic profiles of IEL and their mitogen-specific cytokine (gamma interferon [IFN-gamma] and MIP-1beta) responses (by flow cytometry) and virus-specific cytotoxic T-cell (CTL) activity (by the chromium release assay). Virally infected IEL were detected through the entire course of SIV infection by in situ hybridization. Severe depletion of CD4(+) single-positive and CD4(+)CD8(+) double-positive T cells occurred early in primary SIV infection, which was coincident with an increased prevalence of CD8(+) T cells. This was in contrast to a gradual depletion of CD4(+) T cells in peripheral blood. The CD8(+) IEL were the primary producers of IFN-gamma and MIP-1beta and were found to retain their potential to produce both IFN-gamma and MIP-1beta through the entire course of SIV infection. SIV-specific CTL activity was detected in primary IEL at 1, 2, and 4 weeks post-SIV infection. These results demonstrated that IEL may be involved in generating antiviral immune responses early in SIV infection and in suppressing viral infection thereafter. Alterations in homeostasis in epithelia due to severe CD4(+) T-cell depletion accompanied by changes in the cytokine and chemokine production by IEL may play a role in the enteropathogenesis of SIV infection.

Role of Mucosal Immunity in Herpes Simplex Virus Infection

This study evaluates whether the vaginal mucosal surface of immunized mice can prevent invasion by herpes simplex virus (HSV) and aims to identify immune components that affect immunity after challenge at the vaginal mucosa. Despite the induction of both IgA and IgG vaginal Ab following immunization with recombinant vaccinia virus vectors expressing either glycoproteins B or D, viral infection occurred in most animals even after minimal viral dose challenge. Challenged immune animals, including those genetically unable to generate anti-HSV Ab, survived and showed few if any clinical signs of infection. Experiments with T cell subtype knockout animals and depletion with T cell subset-specific MAb indicated that immunity following vaginal challenge was principally dependent on the function of CD4+ T cells. Our results indicate that anti-HSV vaccines may not provide barrier immunity at the vaginal mucosal site but may be adequate to minimize clinical expression of disease.

Comparison of the immunohistology of mucosa-associated lymphoid tissue in the larynx and lungs in cases of sudden infant death and controls.

The respiratory tract of children in the first two years of life, unlike that of adults, contains bronchus-associated lymphoid tissue (BALT) and larynx-associated lymphoid tissue (LALT) with no differences in frequency between SID and control children. Using immunohistochemical methods we examined the distribution of B, T, CD4+ and CD8+ lymphocytes, HLA-D+ cells, CD68+ macrophages and proliferating cells, comparing bronchus-associated and larynx-associated lymphoid tissue of sudden infant death cases and controls. In all groups the lymphoid tissue was organized in lymphoid follicles and parafollicular areas. With no differences in the cellular composition of BALT and LALT the lymphoid follicles contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably T lymphocytes of both subset types and B lymphocytes were observed in equal numbers in the parafollicular areas in contrast to gut-associated lymphoid tissue. However, the respiratory tract of young children with no differences between SID and controls might play a similar role in mucosal immunity and might function as an inductive site.

Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1.

Beta 7 integrins serve special roles in mucosal immunity. Alpha 4 beta 7-mediated adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs lymphocyte homing to the gut, and alpha E beta 7 mediates binding of lymphocytes to E-cadherin on epithelial cells. Since alpha 4 beta 7 mediates adhesion to MAdCAM-1 but alpha 4 beta 1 does not, we used beta 7/beta 1 chimeras to directly assess the importance of specific regions of beta 7 in MAdCAM-1 binding. We found a region of beta 7 (residues 46-386) that accounts for specificity of alpha 4 beta 7 binding to MAdCAM-1. We also used human/mouse and human/rat chimeric beta 7 subunits to map epitopes recognized by fifteen anti-beta 7 mAbs. Six of seven Abs that block adhesion to MAdCAM-1 and E-cadherin (Fib 21, 22, 27, 30, 504; Act-1) mapped to amino acid residues 176-250. Residues 176-250 lie within the region of beta 7 that specifies MAdCAM-1 binding and also within a region that has a predicted structure homologous to the metal ion-dependent adhesion site (MIDAS) domains of the integrin subunits alpha L and alpha M. Three new Abs that recognize beta 7 in the presence of Mn2+, but not Ca2+, and promote adhesion to MAdCAM-1, mapped to amino acids 46-149. One blocking and five other Abs mapped to other regions (amino acids 387-725). We conclude that a MIDAS-like domain serves a critical role in beta 7 integrin-mediated adhesion.

Larynx-associated lymphoid tissue (LALT) in young children.

Mucosa-associated lymphoid tissue (MALT) plays a central role in mucosal immunity. Whereas the characteristics and function of MALT in the intestine are well established, almost nothing is known about MALT in the larynx. In this study we examined the morphology and the lymphocyte subset composition of MALT in the larynges of children who had died of sudden infant death or various defined traumatic or nontraumatic causes. Organized lymphoid tissue was found in the supraglottic parts of the larynx in nearly 80% of the children in both groups. This lymphoid tissue showed all morphological signs of MALT, such as typical lymphoid follicles with germinal centers, infiltration of the overlying epithelium by lymphocytes, and high endothelial venules (HEV). Thus we will use the term LALT (larynx-associated lymphoid tissue) to refer to this tissue. The lymphoid follicles of LALT contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably, T lymphocytes of both subset types and B lymphocytes were observed in comparable numbers in the parafollicular area. We assume that LALT is a physiological structure of the larynx in young children. The morphology and the distribution of lymphocyte subsets are similar to those of MALT in the human gut. LALT may be a regular part of the mucosal immune system in young children with the role of respiratory inductive site for mucosal immunity.

CD28 and IL-4 but not CD40 play critical regulatory roles in mucosal immunity

CD28 and IL-4 but not CD40 play critical regulatory roles in mucosal immunity

CD28 and IL-4 but not CD40 play critical regulatory roles in mucosal immunity

CD28 and IL-4 but not CD40 play critical regulatory roles in mucosal immunity

HUMAN LUNG SURFACTANT PROTEIN D (SP-D) IS LOCATED IN THE GASTROINTESTINAL TRACT AND IN SALIVA.

Aims: Lung surfactant-associated protein D (SP-D) is an oligomeric molecule with lectin (carbohydrate-binding) domains and collagen regions which has been demonstrated in lung washings. SP-D is believed to be of importance in innate immunity primarily through lectin-like activity and to participate in the formation of lung surfactant and mucus. SP-D is synthesized by pulmonary alveolar type II cells and non-ciliated bronchial cells. Recently, SP-D was demonstrated in the gastric mucosa (Fisher and Mason, 1995). The aim of this study was to investigate the distribution of SP-D throughout the gastrointestinal tract. Methods: Monoclonal antibodies were raised against SP-D and their specificity was confirmed by Western blotting. One antibody was subsequently used for immunohistochemistry. Reverse transcriptase PCR with an antisense SP-D primer and appropriate controls was used to look for SP-D mRNA. The presence of SP-D in saliva was investigated using affinity purification on maltose-agarose columns followed by separation on polyacryl amide gel (SDS-PAGE), Western blotting and detection with antibody. Results: Immunohistochemical localization of SP-D was observed within pulmonary alveolar type II cells, alveolar macrophages and in parotid and submandibular glands. Furthermore, SP-D was found in normal gastric mucosal lining cells and in epithelial cells of small intestinal and colonic tissue (8 subjects). By reverse transcriptase PCR products of approx. 300 base pairs identical to the finding in pulmonary tissue were detected in tissue from parotid gland, stomach, small intestine, colon and pancreas. SP-D was observed in saliva with a molecular mass of 43 kDa under reducing conditions, identical to the findings of SP-D from lung washings. Conclusions: These data indicate that the occurrence of SP-D is not restricted to pulmonary cells, but is found widely distributed at mucosal surfaces. SP-D may play a significant role in mucosal immunity of the gastrointestinal tract.

Lymphoid follicle formation in sinus mucosa of chronic sinusitis

While the presence of mucosa-associated lymphoid tissue (MALT) in the human upper respiratory mucosa is still being debated, it is known that lymphoid follicles (LFs) are present in the mucosa of patients with chronic sinusitis. In the present study, we investigated LFs in chronic sinusitis mucosa samples for the first time immunohistochemically to reveal the frequency and process of lymphoid follicle formation. Forty maxillary sinus mucosa samples from 27 surgical cases were examined. Of the 31 samples, 15 (48.4%) contained primary and/or secondary LFs, 27 (87.1%) contained lymphocyte aggregates (LAs), and 27 (87.1%) contained high endothelial venules (HEVs) located in the LAs and around the LFs. In the inflammatory site above the lesion of the LAs or LFs, respectively, intraepithelial lymphocyte infiltration and a non-ciliated structure or lympho epithelium were seen. In the first phase of diffuse lymphocyte infiltration, CD8+ T cells (suppressor/cytotoxic) were the predominant cells observed in a spreading pattern under the epithelium. In the next phase, while OPD4+ T cells (helper/inducer) were infiltrating, L26+ B cells were gradually aggregating to form lymphocyte clusters (LCs). S-100+ antigen-presenting cells and DRC+ follicular dendritic cells (FDCs) had already appeared during lymphocyte aggregation to promote lymphoid follicle formation. The region of LFs was morphologically divided into the lympho epithelium (LE), the sublympho epithelial area (SLA), the parafollicular area (PFA), and the follicular area (FA). The LE was invaded focally by L26+ B cells and sporadically by UCHL1+ T cells. In the SLA, L26+ B cells and small numbers of OPD4+ T cells were dominant. In the PFA, both OPD4+ and CD8+ T cells were present. The FA consisted of B cells, FDCs, and a few OPD4+ T cells in germinal centers (GCs). In the GCs, we observed VLA-4+ lymphocytes, VCAM-1+ FDCs, IgM+ B cells, and a few IgA+ B cells. On the basis of this study, LFs with lympho epithelium and HEVs are considered prevalent pathological findings in the mucosa humans with chronic sinusitis. Immunohistochemical study revealed the infiltration patterns of T and B lymphocyte subpopulations and FDCs, which clarified the process of LAs, LCs and LFs. This study confirms that LFs are immunologically activated areas that produce plasma cells and are supported by the cellular interaction between FDCs and B cells in their GCs. These MALTs in chronic sinusitis play an important role in mucosal immunity and persistent local inflammation.

Mononuclear cells in salivary glands of normal and isoproterenol-treated rats

The purpose of this study was to analyse the phenotypical distribution of resident cells of the mononuclear phagocyte system in rat salivary glands, and to determine whether isoproterenol induces alterations in macrophage and lymphocyte surface-marker expression. Frozen sections of gland tissues were prepared from five normal rats, and from six rats treated with 20 mg/kg isoproterenol/day for 10 days. A panel of six monoclonal antibodies was used to identify membrane markers associated primarily with monocytes (ED1), mature tissue macrophages (ED2), lymphoid macrophages (ED3), MHC class II (Ia) antigens (OX6), CD5-positive T lymphocytes (OX19), and rat B lymphocytes (OX33). Double-labelling techniques were used to detect the coexpression of ED1/ED2 and OX6/ED2 mononuclear cell markers in the major salivary glands. ED2- positive macrophages were predominant in all three major glands, ranging from 96 cells/0.87 mm 2 field in the parotid gland to 165 cells/0.87 mm 2 in the submandibular. OX19-positive T lymphocytes were rarely observed in submandibular and parotid glands but represented a distinguishing feature of the sublingual. Moderate numbers of ED3-positive macrophages also were detected in sublingual tissues. In the submandibular and parotid glands, isoproterenol resulted in a decrease in ED2-positive cells, but ED2-positive macrophages increased in sublingual glands with isoproterenol. Isoproterenol resulted in a decrease in MHC class II antigen expression on submandibular and sublingual mononuclear cells but an induction of Ia antigen in the parotid gland. Double labelling revealed that isoproterenol induced coexpression of ED1/ED2 markers on mononuclear cells in the submandibular glands, but ED1/ED2-positive cells were absent from other glands. However, coexpression of MHC class II markers on ED2-positive cells in the sublingual and parotid glands of normal rats was frequently observed, with isoproterenol decreasing coexpression in the sublingual gland and increasing it in the parotid. B lymphocytes were not detected in any of the glands examined. These findings indicate that important differences exist in normal resident mononuclear cell subsets among the major salivary glands of the rat. The differential effects of isoproterenol on inflammatory cells may reflect important differences in local salivary gland immunoregulation. Although salivary gland inflammation induced by isoproterenol does not appear to result from immune mechanisms, the rich population of T lymphocytes and ED3-positive macrophages, and presence of MHC class II antigens, suggest that the sublingual gland may function as an immune organ and have a role in mucosal immunity.

Bombesin affects mucosal immunity and gut-associated lymphoid tissue in intravenously fed mice.

Our prior studies show that intravenous (IV) total parenteral nutrition (TPN) produces atrophy of the small intestine-related gut-associated lymphoid tissue and significant decreases in intestinal IgA levels, the major system of mucosal immunity. Others have noted increased small intestinal permeability, bacterial adherence and translocation, and decreased IgA levels in TPN-fed animals. Bombesin, a neuropeptide, may play a regulatory role in mucosal immunity. It is not clear whether bombesin attenuates the TPN-associated gut-associated lymphoid tissue atrophy. To examine the effect of bombesin on gut-associated lymphoid tissue integrity and function during IV TPN feeding. Randomized animal study. A university laboratory. Male ICR mice weighing 25 to 30 g were randomized to chow plus IV saline solution (n = 12), IV TPN (n = 12), or IV TPN plus bombesin (15 micrograms/kg, administered intramuscularly three times a day) (n = 12). Animals were killed after 5 days of receiving the experimental diet. Total small intestinal IgA level was quantified by enzyme-linked immunosorbent assay. Lymphocytes were isolated from Peyer's patches, intraepithelial spaces, and lamina propria and were stained with specific antibodies for B and T cells and for T-cell expression of CD4 and CD8 by flow cytometric analysis. Data were analyzed by analysis of variance. Bombesin prevented the IV TPN decreases in (1) total cell yield and B-cell yield from the Peyer's patches, intraepithelial spaces, and lamina propria; (2) T-cell yield in the intraepithelial spaces and lamina propria; and (3) small intestinal IgA levels. Bombesin also reversed IV TPN decreases in CD4+ and CD8+ T cells in the intraepithelial spaces and Peyer's patches and prevented the decrease in the CD4/CD8 ratio in the lamina propria. Bombesin prevents the TPN-associated atrophy and dysfunction of gut-associated lymphoid tissue, supporting the concept of close neuroimmunologic interaction.

A basement membrane molecule preferentially associated with mucosal post-capillary venules.

B cell lymphomas of mucosa associated lymphoid tissue (MALT-type lymphomas) are a distinct group of tumours which arise in extranodal sites including the stomach, salivary gland, thyroid and lung.1 The onset of lymphomas in the salivary gland and thyroid is known to be preceeded by autoimmune disease, though it is not clear whether the tumour cells themselves in such lymphomas recognise autoantigens.2,3 We have recently shown that low grade MALT-type lymphomas of the gastrointestinal tract recognise autoantigens.4 In this study we have investigated an autoantigen recognised by one such case of low grade B cell gastric lymphoma which we believe may itself have a significant role in mucosal immunity.