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T S Halstensen

Publications and source records attributed to T S Halstensen.

At least 55 records · Page 3Linked to original sources
PubMed1992

Association of subepithelial deposition of activated complement and immunoglobulin G and M response to gluten in celiac disease.

Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (IgG) and M (IgM) antibodies to gluten. Intake of dietary gluten may hence induce local complement activation and mucosal damage. Jejunal tissue sections from adult patients with celiac disease were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and the terminal complement complex (TCC). Subepithelial deposition of TCC was observed in 93% of 28 untreated and in 57% of 23 partly treated study subjects. The immunofluorescence staining intensity was well correlated with the serum level of gluten-specific IgG and IgM (but not IgA), the number of mucosal IgG-producing cells, and the degree of villous atrophy. Similar immune deposits were not observed in 5 successfully treated patients with celiac disease, 5 patients with dermatitis herpetiformis without jejunal villous atrophy, and 90% of 21 control patients with histologically normal jejunal mucosa. Gluten challenge increased the amount of subepithelial TCC and produced additional C3b deposition, suggesting recent complement activation. Ingested gluten might thus, via Ig-mediated subepithelial complement activation, damage the surface epithelium in celiac disease and induce compensatory crypt hyperplasia.

Adolescent↗
PubMed1992

Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract.

Epithelial HLA class II is differentially expressed (DR >> DP) only after birth in salivary glands and small intestinal mucosa, in contrast to class I determinants and secretory component (SC) which appear early in gestation. However, there is a brisk postnatal increase in SC expression along with the class II induction, suggesting stimulation by cytokines from activated immune cells. T lymphocytes remain quite scanty in postnatal salivary glands, and the striking SC and class II expression might reflect a synergistic effect of IFN-gamma and TFN-alpha on immature epithelial cells. Enhanced epithelial expression of both SC and class II in salivary glands from sudden infant death victims could be the effect of immunostimulation caused by an infectious agent. Strikingly upregulated SC and epithelial class II expression (DR > DP > DQ) is seen in various inflammatory lesions such as obstructive sialadenitis, Sjögren's syndrome, chronic gastritis, and celiac disease. IFN-gamma and TNF-alpha are most likely involved as the expression patterns can be reproduced with these cytokines in vitro on colonic epithelial cell lines. However, these molecules of the Ig supergene family do not show a selective response in epithelia of inflammatory lesions because increased expression is also seen for lysozyme, lactoferrin and some other proteins. ICAM-1 can be upregulated on epithelial cells by various cytokines in vitro although the situation remains uncertain in mucosal inflammation. The expression pattern in IBD is complicated by dysplastic epithelial changes leading to reduced SC levels which may thus, in turn, jeopardize the poly-Ig transport mechanism. Epithelial class II molecules appear to have antigen-presenting properties, but the immunopathologic role of their increased expression in inflammatory disease in terms of induction of autoimmunity and/or abrogation of oral tolerance is a matter of continuing dispute.

Animals↗
PubMed1992

Surface epithelium related activation of complement differs in Crohn's disease and ulcerative colitis.

IgG1 and activated complement are colocalised on the colonic epithelial brush border in active ulcerative colitis. To investigate whether such deposition is specific for ulcerative colitis, we examined ethanol fixed mucosal specimens from 18 patients with Crohn's colitis and 14 with terminal ileitis by indirect two colour immunofluorescence staining. Monoclonal antibodies to the IgG subclasses and to neoepitopes of activated complement C3b and the terminal complement complex were used in combination with rabbit antiserum to C1q, C4c or cytokeratin. Granular deposition of C3b and terminal complement complex were observed at the luminal face of the surface epithelium in 10 of 18 patients with Crohn's colitis. Specimens from eight of 14 patients with ileal involvement were intensely stained for activated complement (primarily C3b) within the surface mucus layer. No epithelial IgG, C1q or C4c deposition was observed. The results suggest that early and late phase complement activation takes place at the luminal face of the epithelium in Crohn's disease. The absence of colocalised IgG and complement components involved in the classical activation pathway (C1q and C4c), however, suggest that other immunopathological mechanisms (the alternative pathway?) are primarily involved in Crohn's disease in contrast with ulcerative colitis.

Adolescent↗
PubMed1992

Experimental colonic inflammation and ulceration. Permeation of a water-soluble contrast medium as a measure of 'disease' activity.

The aim of this study was to investigate the permeation of an isosmolar water-soluble X-ray contrast medium (CM) from the unperforated colon after experimental induction of inflammation and ulceration. One hundred and sixty-five male rats were included. In 110 rats 0.25 ml of 40% ethanol + 15 mg or 30 mg trinitrobenzene (TNB) was instilled into the colon, 7-9 cm proximal to the anus, inducing different degrees of inflammation. Fifty-five rats served as controls and had 0.25 ml saline instilled with the same procedure. At 7, 14, 21, and 28 days 3 ml of the non-ionic CM iodixanol was applied as an enema, and subsequently all urine was collected for the next 4 h. High-performance liquid chromatography analyses of the urine showed a positive relation between the severity of inflammation/ulceration in the colonic wall as assessed by a macroscopic damage score and the amount of CM excreted in the urine. Water-soluble contrast media may have prospects of combining functional tests of intestinal membrane dysfunction with segmental exposure control.

Animals↗
PubMed1992

Platelets and vitronectin: immunocytochemical localization and platelet interaction with exogenously added vitronectin.

Vitronectin stores were localized in human platelets by immunofluorescence, confocal laser microscopy, and immunoelectron microscopy. In ultrathin cryosections, the immunogold labelling was mainly observed in the alpha-granules, although occasional immunolabelling of the platelet surface was present. The interaction between thrombin-stimulated platelets and exogenously added vitronectin was also explored. This vitronectin had been purified by heparin-affinity chromatography. Binding of vitronectin to thrombin-stimulated platelets was demonstrated by flow cytometry. The immunoelectron microscopical studies revealed that this binding was mainly restricted to clumps of released alpha-granular material on the platelet surface. The possible significance of the interaction between exogenous vitronectin and released platelet proteins is discussed.

Amino Acid Sequence↗
PubMed1991

Local complement activation in inflammatory bowel disease.

To trace sites for local complement activation in inflammatory bowel disease, an indirect two-colour immunofluorescence method was applied on prewashed and directly ethanol-fixed mucosal specimens from patients with ulcerative colitis, Crohn's colitis, or terminal ileitis. Monoclonal antibodies to the IgG subclasses and to neoepitopes of activated complement C3b and the terminal complement complex (TCC) were used in combination with rabbit antiserum to immunoglobulins and various complement components. Deposits of activated C3b were found on the luminal face of the surface epithelium in the most affected ulcerative colitis specimens from 91% of 23 studied patients, together with cytolytic TCC in 81%. Furthermore, there was a selective deposition of the immunoglobulin G subclass 1 (IgG1) within the epithelial immune complexes in 63% of 11 studied patients. These results suggested that IgG1 autoantibodies to brush-border antigen(s) induce a complement-mediated attack on the epithelium in ulcerative colitis. The epithelial complement deposition seen in Crohn's disease tended to be more granular and was observed in 5 of 10 patients with colitis and in 4 of 10 with ileitis. No co-localization of IgG was observed, suggesting that complement activation had been induced by the alternative pathway. Type III immune reaction may, in addition, take place in both diseases since there was evidence of continuous vascular complement activation in submucosal blood vessels.

Blood Vessels↗
PubMed1991

Cardiac surgery and distribution of the leukocyte L1 protein-calprotectin.

Activated polymorphonuclear leukocytes (PMN) secrete lysosomal enzymes, eicosanoids and toxic oxygen metabolites. In cardiac surgery patients, we measured arterial plasma levels of PMN and L1 (calprotectin), a prominent granulocyte protein, during cardiopulmonary bypass (CPB). The myocardial arterio-venous gradients were evaluated during reperfusion after cold cardioplegic arrest (n = 10). The arterial plasma concentration of L1 increased during CPB from 344 +/- 71 micrograms/l (mean +/- SD) preoperatively to 5221 +/- 1267 micrograms/l at the end of CPB (P less than 0.001). Simultaneously, the number of circulating PMN also increased (from 4.4 +/- 0.4 x 10(9)/l to 9.1 +/- 1.2 x 10(9)/l (P less than 0.05)). There was a positive correlation between the mean number of circulating PMN and the plasma level of L1 at all sampling times during CPB (r = 0.93, P less than 0.05). A coronary sequestration of both L1 (P less than 0.006) and PMN (P less than 0.002) was found after 5 min reperfusion. This was not present at 15 and 30 min reperfusion. The coronary entrapment of L1 and PMN did not covary significantly, and was unrelated to both the time of cardioplegic arrest and the arterial levels of L1 and PMN. In conclusion, the increased plasma concentrations of PMN and L1 during CPB and the coronary sequestration of both PMN and L1 may be factors in the pathogenesis of reperfusion injury of the myocardium.

Adult↗
PubMed1991

Expression of HLA class I and II (DR, DP and DQ) determinants in fetal and postnatal salivary glands.

Fetal (n = 20) and postnatal (n = 40) parotid glands were examined by two-colour immunohistochemistry combining monoclonal and polyclonal antibody reagents to study the expression of HLA class I and II (DR, DP, and DQ), CD45 and CD3. The epithelium lacked class II during fetal life, whereas class I determinants appeared in some acini and most major ducts. Fetal vessels were positive for both class I and class II (mainly DR), suggesting constitutive expression. Some class II-positive (DR greater than DP greater than DQ) histiocytic cells, scattered CD45+ leucocytes, and very few CD3+ T cells were present in the fetal stroma. The epithelium remained DR-negative the first few weeks after birth, but brisk expression was seen subsequently. DP and DQ remained virtually negative in the epithelium throughout the first year. A slight postnatal increase of class II expression (DR greater than DP greater than DQ), along with an apparent decrease in class I, was observed in the endothelium. The number of class II-positive histiocytic cells, CD45+ leucocytes and CD3+ T cells, as well as the proportion of presumably activated (DR+) T cells, increased a few weeks after birth. The local immune system hence seemed to be stimulated by extrinsic factors, but the overall number of T cells nevertheless remained small. Stimuli other than T cell-derived lymphokines, therefore, probably explained the brisk postnatal epithelial DR induction.

Antigens, CD↗
PubMed1990

Human CD8+ intraepithelial T lymphocytes are mainly CD45RA-RB+ and show increased co-expression of CD45R0 in celiac disease.

Expression of various CD45 isoforms (RA, RB and R0) on CD3+, CD4+ and CD8+ intraepithelial and lamina propria T cells was examined in situ by a three-color immunofluorescence technique in jejunal biopsy specimens from 32 patients with celiac disease and 18 controls. The median percentage of CD3+ intraepithelial lymphocytes (IEL) that expressed CD45R0 increased from 52% in controls to 69% in untreated celiac disease (p less than 0.01). Furthermore, the percentages of CD4+ and CD8+ IEL strongly positive for CD45R0 rose respectively from 94% and 24% in controls to 100% and 55% in untreated celiac disease. Conversely, CD45R0 was strongly expressed on most CD3+ lamina propria lymphocytes (LPL) both in control (81%) and diseased (77%-81%) mucosa. A variable fraction of the intraepithelial and lamina propria CD3+ T cells expressed mainly CD45RB (controls, 46% and 20%, respectively; celiac disease, 29% and 15%). Only 2% IEL and 4% LPL were positive for CD45RA. Expression of different CD45R isoforms thus identified three distinct CD8+ T cell subsets in human intestinal mucosa. In addition, our results suggested that antigen-primed CD8+CD45R0+ memory cells accumulate in the jejunal epithelium of patients with untreated celiac disease.

Adolescent↗
PubMed1990

Epithelial deposition of immunoglobulin G1 and activated complement (C3b and terminal complement complex) in ulcerative colitis.

The epithelial destruction seen in ulcerative colitis remains unexplained. Complement activation has been proposed to be involved, but no definite evidence has been available to this end. In the present study, we examined immunohistochemically ulcerative colitis lesions with monoclonal antibodies to activation neoepitopes in the complement component C3b and in the cytolytically active terminal complement complex. Colonic tissue specimens from 23 patients with ulcerative colitis were examined by indirect two-color immunofluorescence staining with monoclonal antibodies to the four human immunoglobulin G subclasses and to activated complement C3b or terminal complement complex. All except two patients had activated C3b deposited apically on the surface epithelium of involved mucosa. Immunoglobulin G1 was found on the epithelium in extensively prewashed specimens from 7 of 11 patients, and a striking colocalization of immunoglobulin G1, C3b, and terminal complement complex was observed in 4. Immune deposits were not observed in 31 noninflamed specimens from the same ulcerative colitis patients. Only 1 of 44 histologically normal mucosae from 17 controls and 1 of 10 colonic adenomas contained some epithelial complement deposits. It is concluded that activated complement is often deposited along the brush border of the surface epithelium in active ulcerative colitis lesions and may be associated with immunoglobulin G1 autoantibody.

Adolescent↗
PubMed1990

Intraepithelial TcR alpha/beta+ lymphocytes express CD45RO more often than the TcR gamma/delta+ counterparts in coeliac disease.

Expression of CD45RO on intraepithelial lymphocytes (IEL) bearing the T-cell receptor (TcR) alpha/beta or gamma/delta was studied in situ by three-colour immunofluorescence on jejunal tissue sections from 21 patients with coeliac disease and eight controls. CD45RA-TcR alpha/beta+ IEL expressed CD45RO significantly more often (75%) than the preferentially expanded TcR gamma/delta+ counterpart (59%). Triple staining for CD3, CD4/8 and CD45RA or CD45RB revealed that all CD3 + 4 - 8 - IEL (taken to be TcR gamma/delta+) expressed CD45RB and none were CD45RA. CD45RO positivity was of the same magnitude (66%) on the predominating monoclonal antibody delta TCS1-reactive fraction of TcR gamma/delta+ cells as on the remainder of the TcR gamma/delta+ subset. These results suggest that gluten exposition in patients with coeliac disease leads to accumulation of CD45RA-, putative antigen-primed memory cells of both TcR phenotypes. The less marked CD45RO expression within the preferentially expanded TcR gamma/delta+ subset of IEL may be of particular biological interest.

Adolescent↗
PubMed1989

Persistent complement activation in submucosal blood vessels of active inflammatory bowel disease: immunohistochemical evidence.

Extensively washed and ethanol-fixed colonic specimens from 10 patients with ulcerative colitis, 3 patients with Crohn's disease of the colon, and 8 histologically normal controls were examined by two-color immunohistochemistry with monoclonal antibody to a neoepitope in the terminal complement complex combined with antiserum to factor VIII-related antigen (von Willebrand's factor), C3c, C3d, or C5. An alternative combination was monoclonal antibody to S-protein and antiserum to C9. Submucosal vessel walls in both normal and diseased colon showed parallel positivity for C3d, C5, C9, terminal complement complex, and S-protein, but the staining intensity and the proportion of positive vessels were significantly higher in inflammatory bowel disease than in controls. In addition, there was significantly more C3c reactivity associated with the terminal complement complex-positive submucosal vessels of active inflammatory bowel disease lesions than in histologically normal colon. Vascular C activation may therefore be a continuous process in active inflammatory bowel disease lesions, presumably related to the degree of inflammation and immune complex formation.

Adolescent↗