Biomedical subjects

B H Toh

Publications and source records attributed to B H Toh.

At least 37 records · Page 2Linked to original sources

PubMed2000

Defining T cell receptors which recognise the immunodominant epitope of the gastric autoantigen, the H/K ATPase beta-subunit.

We have previously shown that autoimmune gastritis can be elicited in mice by immunisation with the gastric parietal cell H/K ATPase alphabeta heterodimer, and, furthermore, have identified the H/K ATPase beta-subunit epitope, H/Kbeta253-277 as the dominant epitope of the gastric H/K ATPase. Using gastric H/K ATPase-immunised mice, here we have generated two T cell hybridomas specific for the H/Kbeta253-277 peptide, namely 4B11.F4.5 and 1E4.C1. Hybridoma 4B11.F4.5 uses Valpha8 and Vbeta8.2 TCR chains and 1E4.C1 uses Valpha9 and V1beta8.3 chains. Although both hybridomas are specific for H/Kbeta253-277, T cell assays using overlapping 14-mers of the 25-mer epitope showed that the two autoreactive TCRs recognise different regions of the 25-mer. The TCR from 1E4.C1 has been used to generate a TCR beta-chain transgenic mouse. >80% of peripheral CD4+ T cells utilise the Vbeta8.3 transgene. As expected, 1E4-TCR beta-chain transgenic mice are susceptible to neonatal thymectomy induced autoimmune gastritis. While none of the 1E4-TCR beta chain transgenic mice spontaneously developed a destructive gastritis, a minority (20%) of the transgenic mice developed a non-invasive and non-destructive gastritis. This suggests that the pathogenic T cells are maintained in a tolerant state in the periphery of the transgenic mice.

Amino Acid Sequence↗

PubMed2000

Novel human autoantibodies to phosphoepitopes on mitotic chromosomal autoantigens (MCAs).

BACKGROUND: Human autoantibodies to proteins of the mitotic apparatus have demonstrated clinical utility and usefulness as molecular probes for identification and characterization of novel autoantigens, as exemplified by autoantibodies to centromere proteins. In contrast, there have been very few reports of autoantibodies with reactivity to antigens located along mitotic chromosome arms, but not in interphase nuclei. The purpose of this study was to identify and characterize autoantibodies with reactivity to mitotic chromosomal antigens (MCAs) located exclusively on mitotic chromosome arms, and to determine if patients with these autoantibodies have common clinical features. METHODS: Routine immunofluorescence screening of serum samples referred for antinuclear antibody investigation over a 10-year period was used to identify autoantibodies to MCAs. MCAs were identified by exclusive immunofluorescence staining of mitotic chromosome arms with no staining of interphase nuclei. MCA-reactive sera were further characterized for patterns of staining on mitotic chromosome arms and sensitivities to chemical and enzymatic treatments, and for one of these sera, its ability to abrogate progression through mitosis when microinjected into cells. RESULTS: Of 60,000 sera screened for antinuclear antibodies by immunofluorescence, we identified three IgG autoantibodies reacting exclusively to MCAs. The anti-MCA autoantibodies did not react with condensed chromatin in spermatozoa or in apoptotic HeLa cells. Reactivity of all three sera was abrogated by treatment with protease, but not RNase, indicating that the MCAs are protein in nature and do not contain RNA epitopes. The three anti-MCA antibodies seem to react to three different antigens because they gave different patterns of staining of chromosome arms, reacted with chromosomes in different stages of mitosis, and displayed different sensitivities to treatment with DNase 1, salt, and phosphatases. Phosphatase treatment suggests that MCA1 and MCA2 contain serine/threonine phosphoepitope(s) and MCA3 tyrosine phosphoepitope(s). Loss of MCA2 reactivity to DNase 1 treatment and its retention after salt extraction suggests that it is a chromosomal scaffold protein. Sensitivity of all three MCAs to acid suggests that they are histone-like or histone-associated proteins. CONCLUSIONS: We report the identification of three novel MCA-reactive sera. Patient diagnoses included discoid lupus erythematosus, chronic lymphocytic leukemia, Sjögren's syndrome, and polymyalgia rheumatica. The reactivity of anti-MCA antibodies with phosphoepitopes is likely to explain restriction of immunofluorescence staining to chromosome arms during mitosis. Microinjection of MCA1-reactive antibodies led to metaphase arrest, without any change in morphology of the mitotic spindle or metaphase chromosomes suggesting that MCA1 may have a role in sister chromatid separation.

Animals↗

PubMed1999

Direct interaction of EEA1 with Rab5b.

The early endosomal autoantigen EEA1 is essential for early endosomal membrane fusion. It binds to endosomes via a C-terminal domain (EEA1-CT). To identify proteins interacting with EEA1-CT, we screened a human brain library in the yeast two-hybrid system. Fourteen clones reacted strongly with EEA1-CT. Sequencing of these clones revealed that they all contained the ORF of the small GTPase, Rab5b. Further two-hybrid analysis suggested that Rab5b also interacts with the N-terminus of EEA1 (EEA1-NT). The interaction of both EEA1-CT and EEA1-NT with Rab5b was confirmed biochemically, and was found to be GTP dependent. Confocal immunofluorescence microscopy indicated that EEA1 colocalizes with Rab5b on early endosomes. Although EEA1-CT and EEA1-NT interacted strongly with wild-type Rab5b in the two-hybrid system, we detected no interaction with wild-type Rab5a, even though GTPase-deficient mutants of both Rab5a and Rab5b interacted equally well with EEA1. This difference could not be explained by differences in intrinsic GTPase activities, as these were found to be very similar. Instead, we speculate that yeast may contain a GTPase-activating protein (GAP) activity that stimulates Rab5a but not Rab5b. In contrast, pig brain cytosol was found to contain a GAP activity that stimulates the GTPase activity of Rab5b in preference to that of Rab5a. These data provide evidence that EEA1 interacts with both Rab5a and Rab5b, and that the GTPase activities of the two proteins are differentially regulated in vivo.

Animals↗

PubMed1999

The endosome fusion regulator early-endosomal autoantigen 1 (EEA1) is a dimer.

EEA1, an early-endosomal protein originally identified as an autoantigen, is essential for endocytic membrane fusion. It interacts with early endosomes via binding to the membrane lipid phosphatidylinositol 3-phosphate (PtdIns3P) and the active form of the small GTPase Rab5. Most of the EEA1 sequence contains heptad repeats characteristic of proteins involved in coiled-coil protein-protein interactions. Here we have investigated the ability of EEA1 to self-interact. Crosslinking of cytosolic and recombinant EEA1 resulted in the disappearance of the 180-kDa monomer in SDS/PAGE and the strong appearance of a approximately 350-kDa crosslinked product. Glycerol gradient centrifugation experiments indicated that native EEA1 had the same hydrodynamic properties as the approximately 350-kDa crosslinked complex. Two-hybrid analysis indicated that N- and C-terminal fragments of EEA1 can interact with themselves, but not with each other, suggesting that EEA1 forms parallel coiled-coil dimers. The ability of the C-terminus of EEA1 to dimerize correlates with its ability to bind to Rab5 and early endosomes, whereas its binding to PtdIns3P is independent of dimerization. These data enable us to propose a model for the quaternary structure of EEA1.

Animals↗

PubMed1999

Gastric H(+),K(+)-adenosine triphosphatase beta subunit is required for normal function, development, and membrane structure of mouse parietal cells.

BACKGROUND & AIMS: Parietal cells of the gastric mucosa contain a complex and extensive secretory membrane system that harbors gastric H(+),K(+)-adenosine triphosphatase (ATPase), the enzyme primarily responsible for acidification of the gastric lumen. We have produced mice deficient in the H(+),K(+)-ATPase beta subunit to determine the role of the protein in the biosynthesis of this membrane system and the biology of gastric mucosa. METHODS: Mice deficient in the H(+), K(+)-ATPase beta subunit were produced by gene targeting. RESULTS: The stomachs of H(+),K(+)-ATPase beta subunit-deficient mice were achlorhydric. Histological and immunocytochemical analyses with antibodies to the H(+),K(+)-ATPase alpha subunit revealed that parietal cell development during ontogeny was retarded in H(+), K(+)-ATPase beta subunit-deficient mice. In 15-day-old mice, cells with secretory canaliculi were observed in wild-type but not in H(+), K(+)-ATPase beta subunit-deficient mice. Parietal cells of H(+), K(+)-ATPase beta subunit-deficient mice 17 days and older contained an abnormal canaliculus that was dilated and contained fewer and shorter microvilli than normal. In older parietal cells, the abnormal canaliculus was massive (25 micrometer in diameter) and contained few microvilli. We did not observe typical tubulovesicular membranes in any parietal cell from H(+),K(+)-ATPase beta subunit-deficient mice. Histopathologic alterations were only observed in the stomach. CONCLUSIONS: The H(+),K(+)-ATPase beta subunit is required for acid-secretory activity of parietal cells in vivo, normal development and cellular homeostasis of the gastric mucosa, and attainment of the normal structure of the secretory membranes.

Animals↗

PubMed1999

Identification of a gastritogenic epitope of the H/K ATPase beta-subunit.

We have previously shown that autoimmune gastritis can be elicited in mice by immunization with the gastric parietal cell H/K ATPase alpha beta heterodimer and that tolerance specifically induced to the H/K ATPase beta-subunit protects mice from the development of gastritis. Here we have identified the immunodominant gastritogenic epitope of the H/K ATPase beta-subunit (H/Kbeta). Epitope mapping was carried out with a panel of 21 overlapping peptides that spanned the entire sequence of the gastric H/K ATPase beta-subunit. T cells from gastric H/K ATPase-immunized mice responded to only one of the overlapping peptides, namely H/Kbeta253-277. Furthermore, a single subcutaneous immunization of 6-week-old BALB/c mice with the ATPase beta-subunit peptides resulted in a T-cell response to only H/Kbeta253-277. Multiple immunization with the overlapping H/K ATPase peptides demonstrated that H/Kbeta253-277 was capable of inducing a mononuclear infiltrate specifically within the gastric mucosa. We conclude that H/Kbeta253-277 is the dominant gastritogenic epitope of the gastric H/K ATPase.

Amino Acid Sequence↗

PubMed1999

Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway.

In epithelial cells, the intracellular pathogen Salmonella typhimurium resides and replicates within a unique cytoplasmic organelle, the Salmonella-containing vacuole (SCV). In vitro studies have shown that the SCV is a dynamic organelle that selectively acquires lysosomal glycoproteins (Igps) without fusing directly with lyosomes. Here, we have investigated early events in SCV biogenesis using immunofluorescence microscopy and epitope-specific flow cytometry. We show that proteins specific to the early endocytic pathway, EEA1 and transferrin receptor (TR), are present on early SCVs. The association of these proteins with SCVs is transient, and both proteins are undetectable at later time points when Igp and vATPase are acquired. Analysis of the fraction of SCVs containing both TR and lamp-1 showed that TR is lost from SCVs as the Igp is acquired, and that these processes occur progressively and not as the result of a single fusion/fission event. These experiments reveal a novel mechanism of SCV biogenesis, involving previously undetected initial interactions with the early endocytic pathway followed by the sequential delivery of Igp. The pathway does not involve interactions with the late endosome/prelysosome and is distinct from traditional phagocytic and endocytic pathways. Our study indicates that intracellular S. typhimurium occupies a unique niche, branching away from the traditional endocytic pathway between the early and late endosomal compartments.

Adenosine Triphosphatases↗

PubMed1999

Species-specific distribution of alpha-galactosyl epitopes on the gastric H/K ATPase beta-subunit: relevance to the binding of human anti-parietal cell autoantibodies.

The gastric H/K ATPase beta-subunit, an abundant glycoprotein of the secretory membranes of gastric parietal cells, is the major autoantigen recognized by human parietal cell autoantibodies in gastric autoimmunity. Our previous studies demonstrated that the human autoantibodies recognize the H/K ATPase beta-subunit from a number of species and that glycosylation of the beta-subunit with complex N-glycans is required for autoantibody binding. The N-glycans of the beta-subunit contain polylactosamine chains. The lactosamine chains of the rabbit beta-subunit are terminated with alpha-linked galactosyl residues (alpha-galactosyl epitope) (Tyagarajan et al., Biochemistry, 1996, 35, 3238-3246). Here we have investigated the expression of alpha-galactosyl epitopes on the H/K ATPase beta-subunit from a number of species. Using the alpha-galactosyl binding lectin, BS1-IB4, and naturally occurring anti-alpha-galactosyl antibodies, we have demonstrated that the rat H/K ATPase beta-subunit also contains terminal alpha-galactosyl residues, but not the beta-subunit from pig, dog, and mouse, indicating species-specific differences in the terminal saccharide sequences of the beta-subunit. We also investigated the potential contribution of the alpha-galactosyl epitopes to the binding by human sera. The reactivity of human pernicious anemia serum with gastric parietal cells could not be inhibited with saccharide inhibitors and, in addition, no binding was observed with normal human sera. We conclude that the H/K ATPase beta-subunit oligosaccharides from rabbit and rat are terminated with alpha-galactosyl epitopes, and although the presence of this epitope does not contribute to binding by human parietal cell autoantibodies at the concentrations routinely used, it is recommended that neither rat or rabbit stomachs be used for screening human sera.

Animals↗

PubMed1999

Routine immunofluorescence detection of Ro/SS-A autoantibody using HEp-2 cells transfected with human 60 kDa Ro/SS-A.

BACKGROUND: Ro/SS-A autoantibodies associated with systemic lupus erythematosus (SLE) and Sjögren syndrome may be missed during routine screening for antinuclear autoantibodies (ANA) by immunofluorescence using HEp-2 cells. AIMS: To investigate the use of HEp-2 cells transfected with human 60 kDa Ro/SS-A for routine detection of these antibodies. METHODS: 10,500 sera were screened at a dilution of 1:200 for Ro/SS-A antibodies, identified by intense immunofluorescence staining in 10-15% of hyperexpressing cells of either the nucleus and nucleolus combined or the nucleus alone. RESULTS: Ro/SS-A antibodies were identified in 160/2100 ANA positive sera (8%), of which seven were ANA negative (titre < 200) and 33 had weak ANA titres (200) in 85-90% of non-hyperexpressing "background" cells. Enzyme linked immunosorbent assay (ELISA) confirmed the presence of Ro/SS-A antibodies in 110 newly diagnosed Ro/SS-A positive sera. Of these, 50 reacted with Ro/SS-A, 51 with Ro/SS-A and La/SS-B, and nine with Ro/SS-A and other extractable nuclear antigen (ENA) specificities. Fifteen sera which did not show Ro/SS-A antibodies by immunofluorescence tested positive for Ro/SS-A by immunodiffusion, counter-immunoelectrophesis, or ELISA; of these, 14 had ANA titres > 200. Clinical data from 95 Ro/SS-A positive patients showed that 52% had SLE, 24% Sjögren syndrome, 8% rheumatoid arthritis, and 16% other diseases. CONCLUSIONS: (1) HEp-2 cells transfected with human 60 kDa Ro/SSA are useful for routine immunofluorescence detection for Ro/SS-A antibodies with a positive predictive value of 100%; (2) sera positive for Ro/SS-A antibodies by immunofluorescence should be tested for ENA by other methods because > 50% of these sera will have another ENA reactivity in addition to Ro/SS-A; (3) detection of Ro/SS-A by immunofluorescence may be missed in the presence of high titre ANAs; (4) with a detection sensitivity of 91%, a negative immunofluorescence results for Ro/SS-A does not exclude the presence of this autoantibody.

Antibodies, Antinuclear↗

PubMed1999

Autoimmune gastritis results in disruption of gastric epithelial cell development.

We have investigated the underlying basis of the lesion in murine autoimmune gastritis, a model of the human disease pernicious anemia. The disease is mediated by T lymphocytes and characterized by selective depletion of parietal and zymogenic cells from the gastric unit (gland) together with gastric epithelial cell hyperplasia. The gastric units of gastritic stomachs contained 2.3-fold more cells than normal and accumulated rapidly dividing, short-lived gastric epithelial stem cells and mucous neck cells. Most of these immature cells failed to differentiate into end-stage cells but rather appeared to die by apoptosis. We also found no correlation between anti-parietal cell autoantibody titers and the degree of gastric pathology, providing further evidence that autoantibodies do not play a direct role in the pathogenesis of gastritis. Taken together, the normal developmental pathways of the gastric mucosa are disrupted in autoimmune gastritis, resulting in an amplification of immature cell types. The differentiation of these immature cells appears to be blocked, contributing to depletion of end-stage cells. This scenario provides an explanation for depletion of not only parietal cells but also zymogenic cells even though they are not directly targeted by the immune system.

Animals↗

PubMed1999

The Golgi-targeting sequence of the peripheral membrane protein p230.

Vesicle transport requires the recruitment of cytosolic proteins to specific membrane compartments. We have previously characterised a brefeldin A-sensitive trans-Golgi network-localised protein (p230) that is associated with a population of non-clathrin-coated vesicles. p230 recycles between the cytosol and the cytoplasmic face of buds/vesicles of trans-Golgi network membranes in a G protein-regulated manner. Identifying the mechanism responsible for Golgi targeting of p230 is important for the elucidation of its function. By transfection of COS cells with deletion mutants of p230 we here demonstrate that the C-terminal domain is necessary for targeting to the Golgi. Furthermore, the C-terminal 98 amino acid domain of p230 attached to the green fluorescent protein (GFP-p230-C98aa) was efficiently Golgi-localised in transfected COS cells. Deletion mutants of GFP-p230-C98aa together with alanine scanning mutagenesis identified a minimum stretch of 42 amino acids that is essential for Golgi targeting, suggesting that the conformation of the domain is critical for efficient targeting. In COS cells expressing high levels of GFP-p230-C98aa fusion protein, endogenous p230 was no longer associated with Golgi membranes, suggesting that the GFP fusion protein and endogenous p230 may compete for the same membrane target structures. The Golgi binding of GFP-p230-C98aa is brefeldin A-sensitive and is regulated by G proteins. These studies have identified a minimal sequence responsible for specific targeting of p230 to the Golgi apparatus, which displays similar membrane binding characteristics to wild-type p230.

Alternative Splicing↗

PubMed1998

Induction of peripheral tolerance in neonatally thymectomized mice by immunization through chemical carcinogen-altered skin.

BALB/c mice thymectomized 3 days after birth (3dnTx) are prone to the development of autoimmune gastritis. As this outcome may be a consequence of altered immunoregulatory mechanisms, we set out to determine the immunological status of these mice and their capacity to acquire antigen-specific peripheral tolerance. The latter was assessed by the capacity of these mice to suppress a contact sensitivity response to 2,4,6-trinitrochlorobenzene (TNCB) following treatment of the skin by the carcinogen, DMBA. The 3dnTx mice had a reduced number of CD4(+) and CD8(+) T cells and a reduced lymphocyte proliferative response to PHA, but a normal contact sensitivity response to TNCB. After treatment of the skin with DMBA these mice failed to develop contact sensitivity to TNCB. Adoptive transfer of splenocytes from these mice to naive mice transfered antigen-specific suppression, irrespective of whether the 3dnTx mice had developed autoimmune gastritis. We conclude that despite thymectomy at day 3 and the attendant immunosuppression, the capacity of BALB/c mice to generate antigen-specific peripheral tolerance to TNCB was retained. These results suggest that precursor T cells which mediate suppression to antigens such as TNCB are present in 3dnTx mice and that these cells are likely to have developed in the thymus and exported to the periphery before 3 days after birth.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

EEA1 links PI(3)K function to Rab5 regulation of endosome fusion.

GTPases and lipid kinases regulate membrane traffic along the endocytic pathway by mechanisms that are not completely understood. Fusion between early endosomes requires phosphatidylinositol-3-OH kinase (PI(3)K) activity as well as the small GTPase Rab5. Excess Rab5-GTP complex restores endosome fusion when PI(3)K is inhibited. Here we identify the early-endosomal autoantigen EEA1 which binds the PI(3)K product phosphatidylinositol-3-phosphate, as a new Rab5 effector that is required for endosome fusion. The association of EEA1 with the endosomal membrane requires Rab5-GTP and PI(3)K activity, and excess Rab5-GTP stabilizes the membrane association of EEA1 even when PI(3)K is inhibited. The identification of EEA1 as a direct Rab5 effector provides a molecular link between PI(3)K and Rab5, and its restricted distribution to early endosomes indicates that EEA1 may confer directionality to Rab5-dependent endocytic transport.

Androstadienes↗

PubMed1998

Transport of residual endocytosed products into terminal lysosomes occurs slowly in rat liver endothelial cells.

Receptor-mediated endocytosis of circulating collagen is a major physiological scavenger function of the liver endothelial cell and an important catabolic event in the complete turnover of this abundant connective tissue protein. In the present study, transport of collagen through the endocytic pathway was investigated in cultured liver endothelial cells. Collagen conjugated to fluorescein isothiocyanate, to allow detection of the ligand by fluorescence and immunoelectron microscopy, was found sequentially in three different organelles that compose the basic degradative endocytic pathway of eukaryotic cells: early endosomes, late endosomes, and terminal lysosomes. Early endosomes were identified as vesicles positive for early endosome antigen 1 (EEA1). Late endosomes were distinguished as structures positive for the late endosomal/lysosomal marker rat lysosomal membrane glycoprotein 120, but negative for EEA1 and lysosomally targeted BSA-gold. Lysosomes were defined by their content of BSA-gold, injected 24 hours before isolation of cells. Coated pits and coated vesicles mediated an extremely rapid internalization. Shortly after internalization and during the first 20 minutes, ligand was found in early endosomes. From 20 minutes on, ligand started to appear in late endosomes (23%), and by 2 hours the transfer was largely complete (82.5%). Only 2.5% of ligand was transferred to the lysosomes after 2 hours, and this number slowly increased to 21% and 53% after 6 and 16 hours, respectively. We conclude that 1) EEA1 is a useful marker for tracing early events of endocytosis in liver endothelial cells; 2) in contrast to the rapid internalization, transit of internalized ligand through early sorting endosomes generally takes from 20 minutes to 2 hours; and 3) exit from the late endosomes is very slow, requiring several hours.

Animals↗

PubMed1998

Autoantibodies to a novel early endosome antigen 1.

Autoantibodies to EEA1, an antigen on early endosomes, were first reported in the serum of a patient with subacute cutaneous lupus erythematosus (SCLE). Here we have examined 38 sera selected for investigation of autoantibodies to EEA1 on the basis of cytoplasmic vesicle-like reactivity by immunofluorescence. Ten of the sera were reactive to a HeLa cell protein of approximately the same M(r) as human EEA1. Eight of these sera belonged to the IgG1 subclass. Five of the sera reacted with fusion proteins incorporating either the amino (from amino acids 1 to 209) or the carboxyl (incorporating the most C-terminal 300 amino acids) terminus of the human EEA1 protein. Antigens reactive with these 5 sera colocalized with internalized transferrin receptors, indicating their association with early endosomes. The other 5 sera which did not react to both fusion proteins did not colocalize with internalized transferrin receptors. We conclude that 5 of the 38 patients (13%) have autoantibodies to EEA1. None of these patients have SCLE, but have generalized joint pain, polyarthritis, rheumatoid arthritis, or circulating rheumatoid factors.

Aged↗

PubMed1998

Spontaneous autoimmune gastritis in C3H/He mice: a new mouse model for gastric autoimmunity.

Autoimmune gastritis is the underlying pathological lesion of pernicious anemia in humans. The lesion is characterized by a chronic inflammatory infiltrate in the gastric mucosa with loss of parietal and zymogenic cells. It is associated with circulating autoantibodies to the gastric H/K-ATPase, the enzyme responsible for acidification of gastric juice. Experimental models of autoimmune gastritis have previously been produced in mice after a variety of manipulations, including thymectomy. Here we report for the first time a spontaneous mouse model of autoimmune gastritis in C3H/He mice. The spontaneous gastritis is also accompanied by circulating autoantibodies to the gastric H/K-ATPase. The spontaneous mouse model should be useful for studies directed toward the immunopathogenesis and treatment of autoimmune gastritis.

Animals↗

PubMed1998

CD4+ T cells, but not CD8+ T cells, are required for the development of experimental autoimmune gastritis.

Murine autoimmune gastritis, induced by neonatal thymectomy, is characterized by a mononuclear infiltrate within the gastric mucosa, loss of parietal and zymogenic cells and circulating autoantibodies to the gastric H/K ATPase. The infiltrate contains both CD4+ and CD8+ T cells. Here we have investigated the roles of CD4+ and CD8+ T cells in the development of gastritis by in vivo treatment with depleting rat anti-CD4 and anti-CD8 monoclonal antibodies. Depletion of CD4+ T cells decreased the incidence of gastric mononuclear infiltrates from 63% (5/8), observed in normal rat immunoglobulin G (IgG)-injected mice, to 8% (1/12) and also abolished the production of antigastric autoantibodies. In contrast, depletion of CD8+ T cells did not reduce the incidence of gastritis. The absence of CD8+ T cells in the infiltrate of the stomach of anti-CD8(+)-treated mice was confirmed by immunocytochemistry. These results argue that neonatal thymectomy-induced autoimmune gastritis is mediated by CD4+ T cells and that CD8+ T cells do not play a significant role in the development of the gastric lesion.

Animals↗

PubMed1997

Pernicious anemia.

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Anemia, Pernicious↗