CD8+CD103+ T cells analogous to intestinal intraepithelial lymphocytes infiltrate the pancreas in chronic pancreatitis

Ebert, M; Ademmer, Karin; Müller, F. E.; Friess, H; Büchler, MarkusW.; Schubert, Walter; Malfertheiner, P.

doi:10.1016/s0016-5085(98)81839-8

Cited by 9 publications

(12 citation statements)

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“…Immunohistological studies of the distribution of T cells in normal and inflamed pancreatic tissue suggest that CD103+ lymphocytes play an important role in the pancreatic epithelium (Ademmer et Experimental Therapeutics Ebert et al, 1998). Staining of serial sections showed that infiltrating T cells included both CD4+ (helper) and CD8+ (cytotoxic) phenotypes and were distributed in the interstitial tissue, periductal regions, or intercalating between the epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Large numbers of lymphocytes were seen in inflamed and malignant pancreas, where CD4+CD103-T cells form the predominant subset. However, CD103+ lymphocytes, generally co-expressing CD8, were observed in the intraepithelial compartment, implying that this subset is analogous to gut IEL Ebert et al, 1998). Induction of CD103 on lymphocytes from peripheral blood was achieved in this study by activation of allospecific T cells in an MLR, followed by culture in the presence of TGFb 1 ; the MLR system was chosen to model antigen-specific activation of large numbers of primary human T cells.…”

Section: Discussionmentioning

confidence: 99%

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T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

et al. 2002

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Pancreatic cancer is an aggressive and potent disease, which is largely resistant to conventional forms of treatment. However, the discovery of antigens associated with pancreatic cancer cells has recently suggested the possibility that immunotherapy might become a specific and effective therapeutic option. T cells within many epithelia, including those of the pancreas, are known to express the aEb7-integrin adhesion molecule, CD103. The only characterised ligand for CD103 is E-cadherin, an epithelial adhesion molecule which exhibits reduced expression in pancreatic cancer. In our study, CD103 was found to be expressed only by activated T cells following exposure to tumour necrosis factor beta 1, a factor produced by many cancer cells. Significantly, the expression of this integrin was restricted mainly to class I major histocompatibility complex-restricted CD8+ T cells. The human pancreatic cancer cell line Panc-1 was transfected with human E-cadherin in order to generate Ecadherin negative (wild type) and positive (transfected) sub-lines. Using a sensitive flow cytometric adhesion assay it was found that the expression of both CD103 (on T cells) and E-cadherin (on cancer cells) was essential for efficient adhesion of activated T cells to pancreatic cancer cells. This adhesion process was inhibited by the addition of antibodies specific for CD103, thereby demonstrating the importance of the CD103?E-cadherin interaction for T-cell adhesion. Using a 51 Crrelease cytotoxicity assay it was found that CD103 expressing T cells lysed E-cadherin expressing Panc-1 target cells following T cell receptor stimulation; addition of antibodies specific for CD103 significantly reduced this lysis. Furthermore, absence of either CD103 from the T cells or E-cadherin expression from the cancer cells resulted in a significant reduction in cancer cell lysis. Therefore, potentially antigenic pancreatic cancer cells could evade a local anti-cancer immune response in vivo as a consequence of their loss of E-cadherin expression; this phenotypic change may also favour metastasis by reducing homotypic adhesion between adjacent cancer cells. We conclude that effective immunotherapy is likely to require upregulation of Ecadherin expression by pancreatic cancer cells or the development of cytotoxic immune cells that are less dependent on this adhesion molecule for efficient effecter function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

et al. 2002

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“…The pathophysiological mechanisms are not fully understood, although components of the immune system have been implicated as key elements in the disease [2] . The pancreas is infi ltrated by lymphocytes in chronic pancreatitis [3][4][5][6] and this appears to at least partially be mediated by upregulation of chemokines in the infl amed gland [7] . In the peripheral blood of chronic pancreatitis patients, several studies have shown a dysregulated distribution of lymphocytes that in some cases is reversed after pancreatic resection [8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Increased central memory T cells in patients with chronic pancreatitis

et al. 2005

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“…Besides the induction of MHC class I and II molecules in chronic pancreatitis, cytotoxic T cells may also infiltrate the pancreas and contribute to its pathogenesis. Interestingly, the degree of lymphocytic infiltration of the pancreas correlates with the severity of pain in patients with chronic pancreatitis [4][5][6]. Chemokines of the C-X-C and of the C-C families, such as IL-8, have also been identified in chronic pancreatitis [7][8][9].…”

Section: Concepts Of the Pathogenesis Of Chronic Pancreatitismentioning

confidence: 99%

Differentiation of Chronic Pancreatitis from Pancreatic Cancer: Recent Advances in Molecular Diagnosis

Ebert

Schandl²,

Schmid³

2001

Dig Dis

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Chronic pancreatitis is an inflammatory disease of the pancreas, characterized by a progressive destruction of the exocrine and endocrine pancreas, leading both to exocrine and endocrine insufficiency. In recent years, our knowledge of this disease has improved, an epidemiological link between chronic pancreatitis and pancreatic cancer has been established, and the molecular alterations underlying their pathogenesis have been partly revealed. Nevertheless, the differentiation of chronic inflammation of the pancreas from cancer of the pancreas remains a great challenge. This overview will point out the present knowledge of the molecular pathogenesis of chronic pancreatitis and pancreatic cancer and will focus on the role of molecular markers for differentiating chronic pancreatitis from pancreatic cancer.

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CD8+CD103+ T cells analogous to intestinal intraepithelial lymphocytes infiltrate the pancreas in chronic pancreatitis

Cited by 9 publications

References 0 publications

T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

Increased central memory T cells in patients with chronic pancreatitis

Differentiation of Chronic Pancreatitis from Pancreatic Cancer: Recent Advances in Molecular Diagnosis

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