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Biomedical subjects

Koichi Tsuneyama

Publications and source records attributed to Koichi Tsuneyama.

At least 37 records · Page 2Linked to original sources
PubMed2005

Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives.

Infiltrating memory T cells play an important role in the destruction of the biliary tract in primary biliary cirrhosis (PBC) and inflammatory chemokines control lymphocyte traffic through their interactions with T cell chemokine receptors. In the present study, we measured plasma levels of chemokines interferon-gamma-inducible protein-10 (IP-10) and monokine induced by gamma interferon (MIG), and also studied the expression of CXCR3 chemokine receptors in 105 subjects, including 53 patients with PBC, 26 first degree relatives and 26 healthy controls. Interestingly, plasma IP-10 and MIG levels in PBC were increased significantly compared to controls and appeared to increase with disease progression. By immunohistochemistry, IP-10 and MIG expressions were evident in the portal areas in PBC. Further, the frequency of CXCR3-expressing cells in peripheral blood was also significantly higher in PBC, and CXCR3-positive cells were also found in the portal areas of diseased livers, primarily on CD4+ cells. Finally, the daughters and sisters of PBC patients also demonstrated increased plasma levels of IP-10 and MIG, but, in contrast, displayed normal frequency of CXCR3+ expressing peripheral blood lymphocytes. Our data imply a role for specific chemokine-chemokine receptor interactions in the pathogenesis of PBC and also highlight the familial risk factor.

Adult↗
PubMed2005

Suppression of Epstein-Barr nuclear antigen 1 (EBNA1) by RNA interference inhibits proliferation of EBV-positive Burkitt's lymphoma cells.

PURPOSE: Epstein-Barr virus (EBV) is associated with the development of several lymphoid and epithelial malignancies, including Burkitt's lymphoma. The EBV latent protein, EBV Nuclear Antigen 1 (EBNA1), is detectable in almost all types of EBV-associated tumors and is essential for replication and maintenance of the latent episome of EBV. We here examined whether the RNA interference (RNAi) technique could be employed to suppress expression of EBNA1 in EBV-positive Burkitt's lymphoma cells. METHODS: A Raji cell line expressing small hairpin RNAs (shRNAs) against EBNA1 was established and EBNA1 mRNA level was determined by real-time RT-PCR analysis. We investigated the effects of EBNA1 silence on lymphoma cell growth and cell cycle progression. RESULTS: Transfection of an EBNA1 RNAi plasmid resulted in substantial loss of EBNA1 mRNA and significantly inhibited proliferation of Raji cells relative to the control plasmid case. Suppression of EBNA1 was also associated with downregulation of EBV oncogene EBNA2, a decreased PCNA labeling index and increased G0/G1 fraction in cell cycle analysis. CONCLUSIONS: These findings point to potential therapeutic applications for vector-mediated siRNA delivery to control EBV-associated malignant disorders.

Apoptosis↗
PubMed2005

Cytoplasmic expression of c-erbB2 in non-small cell lung cancers.

The aim of this study was to investigate the expression of c-erbB2 in non-small cell lung cancers (NSCLCs) with attention both to membranous and cytoplasmic reaction, and to try to elucidate the meaning of cytoplasmic expression of c-erbB2 in NSCLCs. Immunohistochemical c-erbB2 expression and related clinico-pathological features were examined in 312 surgically resected patient tissues of NSCLCs, including 175 cases of adenocarcinoma and 137 cases of squamous cell carcinoma. Immunostaining of inner- and ecto-domain of c-erbB2, mRNA expression and the quantitation of soluble c-erbB2 in cultured media were performed in five NSCLC cell lines. Cytoplasmic expression of c-erbB2 was observed more frequently than membranous, both in patient tissues and cell lines. Neither membranous nor cytoplasmic expression of c-erbB2 was significantly correlated with short outcome in NSCLCs. Membranous c-erbB2 was expressed by both inner and ecto-domain, while cytoplasmic c-erbB2 was expressed by either or both inner and ecto-domain. c-erbB2 mRNA was produced in most cell lines; however, the soluble form was only detectable in a cell line that only presented a membranous c-erbB2. In conclusion, cytoplasmic c-erbB2 of NSCLCs was not a full-length protein only expressed in cellular membrane, but reflected degenerated c-erbB2 fragments with less functional ability.

Adult↗
PubMed2005

Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines.

Most cases of human hepatocellular carcinoma develop after persistent chronic infection with human hepatitis B virus or hepatitis C virus, and host responses are presumed to have major roles in this process. To recapitulate this process, we have developed the mouse model of hepatocellular carcinoma using hepatitis B virus surface antigen transgenic mice. To identify the genes associated with hepatocarcinogenesis in this model, we compared the gene expression patterns between pre-malignant lesions surrounded by hepatocellular carcinoma tissues and control liver tissues by using a fluorescent differential display analysis. Among the genes that were expressed differentially in the pre-malignant lesions, we focused on Pim-3, a member of a proto-oncogene Pim family, because its contribution to hepatocarcinogenesis remains unknown. Moreover, the unavailability of the nucleotide sequence of full-length human Pim-3 cDNA prompted us to clone it from the cDNA library constructed from a human hepatoma cell line, HepG2. The obtained 2,392 bp human Pim-3 cDNA encodes a predicted open reading frame consisting of 326 amino acids. Pim-3 mRNA was selectively expressed in human hepatoma cell lines, but not in normal liver tissues. Moreover, Pim-3 protein was detected in human hepatocellular carcinoma tissues and cell lines but not in normal hepatocytes. Furthermore, cell proliferation was attenuated and apoptosis was enhanced in human hepatoma cell lines by the ablation of Pim-3 gene with RNA interference. These observations suggest that aberrantly expressed Pim-3 can cause autonomous cell proliferation or prevent apoptosis in hepatoma cell lines.

Amino Acid Sequence↗
PubMed2005

Are bile duct lesions of primary biliary cirrhosis distinguishable from those of autoimmune hepatitis and chronic viral hepatitis? Interobserver histological agreement on trimmed bile ducts.

BACKGROUND: Primary biliary cirrhosis (PBC) is histopathologically characterized by chronic nonsuppurative destructive cholangitis and ductopenia of interlobular bile ducts. Bile duct injury is also often encountered in chronic viral hepatitis (CVH) and in autoimmune hepatitis (AIH). METHODS: In this study, we performed interobserver agreement analysis on 90 injured bile ducts from liver specimens of PBC (17 cases), CVH (26 cases), and AIH (18 cases), with 30 bile ducts chosen from each disease group. Digital images of bile ducts with minimal periductal elements were recorded in CD-ROM format and sent to 14 observers (six special hepatopathologists, four local hepatopathologists, and four general pathologists). We analyzed the following issues: (1) diagnostic accuracy of PBC, based only on bile duct lesions; (2) classification of bile duct lesions in AIH cases as destructive cholangitis equivalent to PBC-associated injury, or not. RESULTS: The diagnostic accuracy of PBC cases with severe bile duct injuries was very high (over 80%), although the accuracy in cases with only mild bile duct injuries was low (50% or less). For AIH, each observer classified 9 of the 30 bile ducts, on average, as destructive cholangitis. CONCLUSIONS: This study revealed that 66.9% of PBC cases could be diagnosed based on trimmed bile ducts alone. Bile duct injury similar to that in PBC could be encountered in AIH.

Bile Ducts↗
PubMed2005

Correlation between DNA alterations and p53 and p16 protein expression in cancer cell lines.

To investigate the interaction between DNA abnormalities, p53 and p16 gene mutations, and methylation and protein expression, 20 cancer cell lines were examined by Western blotting. A clear relation was found to exist between p53 accumulation and mutation status. Of 20 cell lines examined, 14 demonstrated p53 homozygous mutations in exons 3-10, including 12 missense mutations, one nonsense mutation, and one frameshift mutation. Overexpression of p53 was always linked to missense mutations in exons 6-8. Intermediate expression of p53 was noted in cells with missense mutations or polymorphism to proline at codon 72 in exons 4-5, whereas there was slight or no visible expression in wild type cells and in cells with nonsense and frameshift mutations. DNA aberration in the p16 promoter gene correlated significantly with protein expression of the p16 suppressor gene. Overexpression was noted in six cell lines, intermediate expression in two, and slight or no visible expression in 12. Methylation-caused disappearance of p16 protein was noted in 40% (8/20) of the cell lines. Of six cell lines overexpressing p16 protein, two could be amplified with primers for both unmethylated and methylated forms in a methylation-specific RCP analysis. One cell line with no visible expression could also be amplified with both primers. Overexpression or disappearance of p16 protein may readily occur when one of two alleles has been methylated.

Biomarkers, Tumor↗
PubMed2005

Expression profiling of endogenous secretory receptor for advanced glycation end products in human organs.

The receptor for advanced glycation end products (RAGE) is a cell surface multiligand receptor of the immunoglobulin superfamily, which participates in physiological and pathological processes such as neuronal development, diabetes, inflammation, neurodegenerative disorders, and cancer. A novel splice variant of RAGE-endogenous secretory decoy form (esRAGE) was recently identified and is thought to be a prospective candidate to modify these RAGE-associated conditions. Here, we investigated the expression and distribution of esRAGE and RAGE proteins with domain-specific antibodies. We studied a wide variety of adult normal human preparations obtained from surgical and autopsy specimens using a tissue microarray technique. The results revealed that esRAGE was widely distributed and we classified its expression into four patterns. In pattern A, the cytoplasm is stained diffusely in neurons, vascular endothelium, pneumocytes, mesothelium, pancreatic beta cells, and macrophages/monocytes. In pattern B, dot-like granules are stained in the supranuclear regions facing the luminal surface of the bile ducts, salivary glands, digestive tracts, renal tubules, prostate, skin, thyroid, and bronchioles. Pattern C is represented by diffuse staining in the stromal area of the arterial walls. Pattern D shows diffuse and strong staining of secreted materials such as thyroidal colloid, crystals in renal tubular lumen, and glandular lumen in prostate. This study provides, for the first time, a histopathological basis for understanding the physiological roles of esRAGE in humans, and will contribute to elucidating the participation of esRAGE in pathological processes and to exploring novel diagnostic and therapeutic concepts.

Glycation End Products, Advanced↗
PubMed2005

Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Küttner's tumor).

Chronic sclerosing sialadenitis (CSS) is a cryptogenic tumor-like condition of the salivary gland(s). While immune-mediated processes are suspected in its pathogenesis, and CSS is occasionally reported to be associated with sclerosing pancreatitis, an IgG4-related disease, the exact immunopathologic processes of CSS remain speculative. In this study, we examined the clinicopathologic findings of CSS (12 cases) in comparison with sialolithiasis (8 cases) and Sjogren's syndrome (13 cases), and tried to clarify whether CSS is an IgG4-related disease or not. Submandibular gland(s) were affected in all cases of CSS. CSS cases could be divided into two types: 5 cases were associated with sclerosing lesions in extrasalivary glandular tissue (systemic type), while only salivary gland(s) were affected in the remaining 7 cases (localized type). In the former type, which showed male predominance, bilateral salivary glands were frequently affected, and eosinophilia and elevations of gamma-globulin and IgG in serum were frequently found. Histologically, all cases of CSS showed marked lymphoplasmacytic infiltration admixed with fibrosis and the destruction of glandular lobules. Obliterative phlebitis was found in the affected salivary glands in all cases of CSS. Immunohistochemically, the proportion of IgG4/IgG-positive plasma cells was more than 45% in CSS, while it was less than 5% in controls. The resemblance of the clinicopathologic features of CSS with those of sclerosing pancreatitis suggests the participation of a similar immunopathologic process with IgG4 disturbance in CSS. The abundance of IgG4-positive plasma cells in the lesions would be useful for distinguishing CSS from other forms of sialadenitis.

Aged↗
PubMed2004

Improved 1-h rapid immunostaining method using intermittent microwave irradiation: practicability based on 5 years application in Toyama Medical and Pharmaceutical University Hospital.

Immunostaining depending on antigen-antibody specificity is the commonest approach for determining the localization of specific antigens in tissue sections. This procedure is applicable not only with frozen or specially fixed samples, but also has proved reliable with formalin-fixed paraffin-embedded tissue sections through improvement of antigen-retrieval. Immunostaining is thus firmly established as a tool for diagnostic pathology and in our institute multiple antibodies are applied for 13-15% of the cases examined, as well as H and E staining. With the standard approach, approximately 3 h is necessary from the beginning of deparaffinization till covering sections with the Envision system. We utilized intermittent microwave irradiation for 10 min during hybridization with primary and secondary antibodies in a special moist-chamber, to achieve all immunostaining steps within 1 h in 178 primary antibodies frequently used for diagnostic pathology. According to our 5 years experience, such microwave irradiation not only obtained significant specific staining for enhancing the specificity of antigen-antibody reactions, but also inhibited nonspecific binding. We present herein the details of the methodology and recommendations for its application with particular primary antibodies. This method can contribute to savings in time and energy, allowing pathologists to rapidly obtain diagnostic information.

Antibodies, Monoclonal↗
PubMed2004

IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis: do they belong to a spectrum of sclerosing pancreatitis?

Sclerosing cholangitis (SC) is a heterogeneous disease entity. Different etiologies such as choledocholithiasis, biliary tumor, or pericholangitis can manifest as SC. Hepatic inflammatory pseudotumor (IP) is rarely associated with SC (sclerosing cholangitis associated with hepatic inflammatory pseudotumor; SC-hepatic IP), but sclerosing pancreatitis (SP) is not infrequently associated with bile duct lesions (sclerosing pancreatitis-associated sclerosing cholangitis; SP-SC). In this study, we compared the histologic changes of hepatic hilar and extrahepatic bile duct lesions of SC (7 cases), SC-hepatic IP (5 cases), SP-SC (5 cases), and typical primary sclerosing cholangitis (PSC) (5 cases). Histologically, all SP-SC cases showed extensive and dense fibrosis with marked lymphoplasmacytic infiltration, many eosinophils, and obliterative phlebitis. Four cases of SC showed bile duct lesions similar to those of SP-SC, whereas other three cases of SC showed milder lymphoplasmacytic infiltration, scant eosinophilic cell infiltration, and no obliterative phlebitis. All SC-hepatic IP cases showed bile duct lesions identical to those of SP-SC. Immunohistochemically, many IgG4-positive plasma cells were found in the bile duct lesions of all SP-SC cases, 4 SC cases with marked lymphoplasmacytic infiltration, and all SC-hepatic IP cases. By contrast, IgG4-positive plasma cells were scarce or hardly found in the remaining 3 SC cases and all PSC cases. In conclusion, 4 SC cases and all SC-hepatic IP cases showed bile duct lesions identical to those of SP-SC, suggesting that these three conditions may be a single disease entity. Their pathogenesis may be similar or closely related to that of SP, and in that respect they may represent an IgG4-related biliary disease. They may respond to steroid therapy as SP does.

Adult↗
PubMed2004

Expression of MAGE-A3 in intrahepatic cholangiocarcinoma and its precursor lesions.

MAGE-A3 antigen is known to be neo-expressed in a large proportion of tumors but not detectable in normal tissues, and could be a target antigen recognized by autologous cytotoxic T lymphocytes. In the present study, the expression of MAGE-A3 at protein and mRNA levels was examined in intrahepatic cholangiocarcinoma (ICC) and its precursor lesions. Carcinomatous and dysplastic biliary cells expressed MAGE-A3 in their cytoplasm diffusely, although there was no MAGE-A3 expression in normal and hyperplastic biliary cells. MAGE-A3 was expressed in one of 10 cases (10%) of low-grade dysplasia, four of 13 (31%) cases of high-grade dysplasia/in situ carcinoma, and 32 of 68 invasive ICC cases (47%), respectively. The MAGE-A3 mRNA expression pattern was similar to that of MAGE-A3 protein. The incidence and intensity of MAGE-A3 expression increased along the progression of biliary neoplasia (P < 0.05). There was no correlation between MAGE-3 expression and histological differentiation or anatomical locations of invasive ICC. MAGE-A3 is a promising target molecule for the specific immunotherapy of ICC.

Adult↗
PubMed2004

Site-characteristic expression and induction of trefoil factor family 1, 2 and 3 and malignant brain tumor-1 in normal and diseased intrahepatic bile ducts relates to biliary pathophysiology.

BACKGROUND/AIM: Trefoil factor family (TFF)1,2,3 are involved in a homeostasis/repair process of mucosal epithelia. In this study, the significance of TFF family and deleted in the malignant brain tumor-1 (DMBT1), a putative receptor of TFF2, in the intrahepatic biliary tree was investigated in normal and diseased livers. MATERIALS AND METHODS: Expression of TFF1,2,3 and DMBT1 were examined immunohistochemically in primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), extrahepatic biliary obstruction (EBO), and normal livers. RESULTS: In normal livers, TFF1,3 and DMBT1 were infrequently detectable in large and rarely in small bile ducts, respectively. TFF2 was not detectable in large bile ducts. In large bile duct diseases (PSC and EBO), expression of TFF3 and DMBT1 were increased. In small bile duct diseases (PBC and CVH), expression of TFF2/DMBT1 was induced in moderately to severely damaged ducts irrespective of etiology. CONCLUSION: The intrahepatic biliary tree shows a site-characteristic expression and induction of TFF1,2,3 and DMBT1. In large bile ducts, TFF1,3 were constitutively expressed and increased in pathologic bile ducts. In small bile ducts, TFF2/DMBT1 is induced in damaged ducts irrespective of etiologies. However, the cytoprotective/repair property of TFF2/DMBT1 may not be enough to prevent the following bile duct loss in PBC.

Agglutinins↗
PubMed2003

The pathogenic roles of tumor necrosis factor receptor p55 in acetaminophen-induced liver injury in mice.

Acetaminophen (APAP) causes a massive production of intrahepatic tumor necrosis factor alpha (TNF-alpha). However, it still remains elusive regarding the roles of TNF-alpha in APAP-induced liver injury. Hence, we examined pathogenic roles of the TNF-alpha-TNF receptor with a molecular weight of 55 kDa (TNF-Rp55) axis in APAP-induced hepatotoxicity using TNF-Rp55-deficient [TNF-Rp55-knockout (KO)] mice. When wild-type (WT) BALB/c and TNF-Rp55-KO mice were intraperitoneally injected with a lethal dose of APAP (750 mg/kg), the mortality of TNF-Rp55-KO mice was marginally but significantly reduced compared with WT mice. Upon treatment with a nonlethal dose (600 mg/kg), WT mice exhibited an increase in serum transaminase levels. Histopathologically, centrilobular hepatic necrosis with leukocyte infiltration was evident at 10 and 24 h after APAP challenge. Moreover, mRNA expression of adhesion molecules, several chemokines, interferon-gamma (IFN-gamma), and inducible nitric oxide synthase (iNOS) was enhanced in the liver. On the contrary, serum transaminase elevation and histopathological changes were attenuated in TNF-Rp55-KO mice injected with APAP (600 mg/kg). The gene expression of all molecules except for IFN-gamma and iNOS was significantly attenuated in TNF-Rp55-KO mice. Moreover, anti-TNF-alpha neutralizing antibodies alleviated liver injury when administered at 2 or 8 h after but not at 1 h before APAP challenge to WT mice. Collectively, the TNF-alpha-TNF-Rp55 axis has pathogenic roles in APAP-induced liver failure.

Acetaminophen↗
PubMed2003

Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis.

BACKGROUND & AIMS: Previous work has suggested that CD4+ CD28- or costimulation-independent T cells are increased in autoimmune diseases. In this study, we compared frequency and qualitative characteristics of autoreactive costimulation-independent or CD4+ CD28- T cells in primary biliary cirrhosis (PBC) by taking advantage of the well-defined immunodominant autoepitope of the E2 component of pyruvate dehydrogenase (PDC-E2). METHODS: We determined the frequency of costimulation-independent autoreactive T cells that respond to PDC-E2 163-176 and the frequency of CD4+ CD28- T cells. Finally, we determined the role of biliary epithelial cells (BEC) as both an antigen-presenting cell or, alternatively, as a target cell for T-cell-mediated cytotoxicity. RESULTS: The precursor frequency of costimulation-independent CD4+ T cells that respond to PDC-E2 163-176 and the frequency of CD4+ CD28- T cells were dramatically elevated in PBC. Furthermore, 2 types of T-cell clones that respond to PDC-E2 163-176 emerged from this study. One type was costimulation dependent and the other costimulation independent. Both types of clones lyse BEC in a similar effector target (E/T) ratio distribution. However, BEC did not help the proliferation of any T-cell clones. Furthermore, costimulation-independent T-cell clones do not become anergic by BEC. CONCLUSIONS: In PBC, costimulation-independent autoreactive T cells, which do not become anergic, increase and maintain the autoimmune response. In controls, although autoantigens are expressed on BEC and autoantigen-reactive T cells exist around BEC, autoantigen-reactive T cells are costimulation dependent and will become anergic and maintain peripheral tolerance.

Antigen-Presenting Cells↗
PubMed2003

Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor.

Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (HC-CC) are known to arise occasionally in hepatitis-related cirrhosis, although their clinicopathological features remain unclarified. In this study, we characterized the ICC (9 cases) and ICC elements of HC-CC (11 cases) arising in nonbiliary cirrhosis. Thirty-three hepatocellular carcinomas (HCC) associated with nonbiliary cirrhosis and 24 ICC without cirrhosis were used as controls. Prominent neutrophilic infiltration was frequent in ICC with cirrhosis (78%) and ICC elements of combined HC-CC (72%). Neutrophilic infiltration-related cytokines (interleukin 8, granulocyte colony-stimulating factor [G-CSF], and granulocyte macrophage colony-stimulating factor [GM-CSF]) were expressed frequently and intensely in carcinoma cells of ICC with cirrhosis (40%, 80%, and 60%, respectively) and in ICC elements of the combined one (13%, 38%, and 63%, respectively). Interleukin 8 was expressed in 18% of ICC without cirrhosis, irrespective of neutrophilic infiltration. Neutrophilic infiltration and expression of G-CSF and GM-CSF were in parallel (P < 0.05). G-CSF and GM-CSF mRNA were detected by RT-PCR in tissue specimens expressing G-CSF and GM-CSF at the protein level. Such neutrophilic infiltration and expression of G-CSF and GM-CSF were not evident in controls. The expressions of c-kit and c-Met, as a hematopoietic and hepatic stem cell marker, were seen frequently in ICC with cirrhosis (80% and 80%, respectively) and ICC elements of the combined one (63% and 50%, respectively). The present study revealed that the frequent expression of G-CSF and GM-CSF is a characteristic of ICC with cirrhosis and ICC in combined carcinoma, probably representing a phenotype of fetal hepatic parenchymal cell. The expression of these cytokines may be causally related to prominent neutrophilic infiltration.

Aged↗
PubMed2003

Expression of deleted in malignant brain tumor-1 (DMBT1) molecule in biliary epithelium is augmented in hepatolithiasis: possible participation in lithogenesis.

Deleted in malignant brain tumor-1 (DMBT1) is a mucin-like molecule participating in mucosal immune defense. Given that bovine gallbladder mucin, which accelerates cholesterol crystallization, is a DMBT1 homolog, DMBT1 expression was examined immunohistochemically in biliary epithelial cells in livers with hepatolithiasis (N = 25), primary sclerosing cholangitis (N = 7), large bile duct obstruction (N = 12), and control normal livers (N = 10). DMBT1 protein was determined in the hepatic bile samples of hepatolithiasis (N = 12) and other hepatobiliary diseases (N = 8) by immunoblot. While DMBT1 was faintly expressed in normal livers (20%), it was significantly augmented in hepatolithiasis (76%) (P < 0.05). DMBT1 was mildly expressed in primary sclerosing cholangitis and large bile duct obstruction. DMBT1 protein was detected frequently in hepatic bile samples of hepatolithiasis (50%) (P < 0.05), but in the other bile samples. The percentage of cholesterol in intrahepatic calculi was significantly higher in the patients with DMBT1-positive bile. Augmented expression and secretion of DMBT1 in intrahepatic large bile ducts in hepatolithiasis suggests its role in lithogenesis.

Agglutinins↗
PubMed2003

Accumulating CD57 + CD3 + natural killer T cells are related to intrahepatic bile duct lesions in primary biliary cirrhosis.

BACKGROUND: Some populations of extrathymic T cells including natural killer T (NKT) cells are involved in autoimmune diseases. In particular, a deficiency of NKT cells has been implicated in human systemic sclerosis. Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the selective destruction of intrahepatic small bile ducts and the formation of granulomas. It is generally believed that cellular immune mechanisms, particularly T cells, cause the bile duct damage in PBC. METHODS: In this study, to investigate the unique population of extrathymic T cells in PBC, we examined the T cell receptor (TCR) V alpha 24-J alpha Q gene and CD57 + CD3 + cells corresponding to the major genotype and one of the phenotypes of NKT cells, respectively. RESULTS: By reverse transcription-polymerase chain reaction (RT-PCR), amplicons of the V alpha 24-J alpha Q gene fragment in liver tissues of PBC were found to be similar to those of control diseased livers, demonstrating that there was no distinct deficiency of V alpha 24-J alpha Q + NKT cells in PBC. Immunohistochemistry for CD57 and CD3 revealed the CD57 + CD3 + cells to be distributed in portal tracts and hepatic parenchyma in all cases studied, but the numbers of these cells were increased within portal tracts in PBC, in particular around injured interlobular bile ducts, compared to other diseased and normal livers. CONCLUSION: This indicates that an immune disturbance induced by a selective reduction of V alpha 24-J alpha Q + NKT cells is unlikely to occur in PBC. Inversely, it can be postulated that auto aggressive CD57 + CD3 + NKT cells are recruited to regulate the altered immunity of the periductal microenvironment in PBC.

Aged↗