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

Kamihira, Takashi; Shimoda, Shinji; Harada, Kenichi; Kawano, Akira; Handa, Mizuki; Baba, Eishi; Tsuneyama, Koichi; Nakamura, Minoru; Ishibashi, Hiromi; Nakanuma, Yasuni; Gershwin, M. Eric; Harada, Mine

doi:10.1016/j.gastro.2003.07.013

Cited by 57 publications

(53 citation statements)

References 40 publications

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“…46 Furthermore, autoreactive T cells against PDC-E2 are also detectable in the serum and liver in PBC. 47 CD4 ϩ T cells, especially CD4 ϩ and CD28 Ϫ T cells recognizing PDC-E2 and CD8 ϩ T cells recognizing PDC-E2, were increased in number in the peripheral blood and liver tissue of PBC livers, 24,47 and these autoreactive T cells may be cytotoxic and responsible for immune-mediated BEC damage. This finding and the circumstantial evidences given above support that idea that fractalkine and CX3CR1 expression are relevant to duct injury in PBC livers via autoreactive and cytotoxic T-cell migration.…”

Section: Discussionmentioning

confidence: 93%

“…One human intrahepatic cholangiocarcinoma cell line, HuCC-T1 23 (JCRB0425; Health Science Research Resources Bank, Osaka, Japan), and one nonneoplastic human intrahepatic BEC cell line (HIBEC), primary culture, originating from an explanted liver with hepatitis C virus-related cirrhosis 24 were used. These cells grew on culture dishes with standard medium, RPMI 1640 medium (Gibco, Rockville, MD) with 10% fetal bovine serum for HuCC-T1, and DMEM/F12 (Gibco) with 10% fetal calf serum for HIBEC.…”

Section: Cell Culturementioning

confidence: 99%

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Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts†

et al. 2005

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Fractalkine is a chemokine with both chemoattractant and cell-adhesive functions, and in the intestine it is involved with its receptor CX3CR1 in the chemoattraction and recruitment of intraepithelial lymphocytes. We examined the pathophysiological roles of fractalkine and CX3CR1 in normal and diseased bile ducts. Expression of fractalkine and CX3CR1 were examined in liver tissues from patients with primary biliary cirrhosis (17 cases) and controls (9 cases of primary sclerosing cholangitis, 10 cases of extrahepatic biliary obstruction, 20 cases of chronic viral hepatitis C, and 18 cases of histologically normal livers). Expression of fractalkine in biliary epithelial cells (BECs) in response to cytokine treatments was examined using a human cholangiocarcinoma cell line (HuCC-T1) and human intrahepatic BEC line. The chemotaxis of CX3CR1-expressing monocytes (THP-1) toward fractalkine was assayed using chemotaxis chambers. Fractalkine messenger RNA/protein were expressed on BECs of normal and diseased bile ducts, and their expression was upregulated in injured bile ducts of primary biliary cirrhosis. CX3CR1 was expressed on infiltrating mononuclear cells in portal tracts and on CD3

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Section: Discussionmentioning

confidence: 93%

Section: Cell Culturementioning

confidence: 99%

Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts†

et al. 2005

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“…Using methods previously described, 15 we isolated and characterized 2 human autoreactive TCCs, coined HT7 and HK15, from 2 HLA-DR53 patients with early-stage PBC. Peripheral blood mononuclear cells (PBMCs) from these 2 patients were placed in RPMI medium containing 10% fetal calf serum and repeatedly stimulated by PDC-E2 163-176 -pulsed irradiated autologous PBMCs.…”

Section: Generation Of Autoreactive Tccs That Respond Tomentioning

confidence: 99%

“…These 2 TCCs were CD3 ϩ , CD4 ϩ , CD8 Ϫ , CD45RO ϩ , and TCR␣␤ ϩ and produced a Th1-type cytokine profile, expressing high levels of IFN␥ and low levels of IL-4, and recognized PDC-E2 163-176 in an HLA-DR53-restricted manner. 15 Both clones recognize amino acids 163-176 (GDLLAEIETDKATI) in PDC-E2 within the context of HLA-DR53. The antigenic peptide used in this study, PDC-E2 163-176, was synthesized on a solid phase simultaneous multiple peptide synthesizer (PSSM-8, Shimadzu, Kyoto, Japan), based on previously described Fmoc strategy.…”

Section: Generation Of Autoreactive Tccs That Respond Tomentioning

confidence: 99%

“…In fact, our data illustrated that BECs regulate the proliferation of costimulation-dependent TCCs after rendering them anergic. 15 This latter finding was unique and led us to investigate the mechanism of this regulatory effect of BECs in detail. We report herein that BECs regulate autoreactive T cells even in the presence of professional APCs through the direct action of several inhibitory molecules, including ligands of programmed death 1 (PD-1) (PD-1 ligands 1 and 2 [PD-L1 and PD-L2]) and through the indirect action of prostaglandin E2 (PG-E2).…”

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confidence: 99%

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Biliary epithelial cells regulate autoreactive T cells: Implications for biliary-specific diseases

et al. 2005

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The biliary epithelial cell (BEC) is the target for several human immune mediated liver diseases, including primary biliary cirrhosis, but it is not always clear whether the BEC functions as an accessory cell or an antigen presenting cell, although it is well documented that BECs express high levels of human leukocyte antigen Class II, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3. To examine this issue, we established autoreactive T-cell clones from human leukocyte antigen-DR53 patients with primary biliary cirrhosis and characterized BEC function as a function of the ability of BECs to regulate T-cell activation. We report herein that BEC-mediated T-cell activation occurs partially via programmed death 1 ligands in a cell-contact-dependent manner. Further, such activation occurs via prostaglandin E2 production in a cell-contact-independent fashion. Moreover, the production of prostaglandin E2 was partially controlled by interleukin-1␤ and tumor necrosis factor ␣.

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Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints

Schett¹,

Kiechl²,

Bonora³

et al. 2009

Arthritis & Rheumatism

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Objective. Osteoarthritis (OA) is a leading cause of pain and physical disability in middle-aged and older individuals. We undertook this study to determine predictors of the development of severe OA, apart from age and overweight.Methods. Joint replacement surgery due to severe hip or knee OA was recorded over a 15-year period in the prospective Bruneck cohort study. Demographic characteristics and lifestyle and biochemical variables, including the level of soluble vascular cell adhesion molecule 1 (VCAM-1), were assessed at the 1990 baseline visit and tested as predictors of joint replacement surgery.Results. Between 1990 and 2005, hip or knee joint replacement due to OA was performed in 60 subjects. VCAM-1 level emerged as a highly significant predictor of the risk of joint replacement surgery. Intervention rates were 1.9, 4.2, and 10.1 per 1,000 person-years in the first, second, and third tertiles, of the VCAM-1 level, respectively. In multivariable logistic regression analysis, the adjusted relative risk of joint replacement surgery in the highest versus the lowest tertile group of VCAM-1 level was 3.9 (95% confidence interval 1.7-8.7) (P < 0.001). Findings were robust in various sensitivity analyses and were consistent in subgroups. Addition of the VCAM-1 level to a risk model already including age, sex, and body mass index resulted in significant gains in model discrimination (C statistic) and calibration and in more accurate risk classification of individual participants.Conclusion. The level of soluble VCAM-1 emerged as a strong and independent predictor of the risk of hip and knee joint replacement due to severe OA. If our findings can be reproduced in other epidemiologic cohorts, they will assist in routine risk classification and will contribute to a better understanding of the etiology of OA.

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

Cited by 57 publications

References 40 publications

Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts†

Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts†

Biliary epithelial cells regulate autoreactive T cells: Implications for biliary-specific diseases

Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints

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