Increased Expression of Hla-DR Antigens on Renal Tubular Cells in Renal Transplants: Relevance to the Rejection Response

Hall, Bruce M.; Duggin, Geoffrey G.; Philips, Jeanette; Bishop, G. Alex; Horvath, J. S.; Tiller, D. J.

doi:10.1016/s0140-6736(84)90297-6

Cited by 178 publications

(65 citation statements)

References 28 publications

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“…In vivo, induced expression ofMHC antigens has been reported for a number of other inflammatory sites, including transplanted kidneys (27), biliary epithelium in PBC (4), thyroid epithelium in Graves' disease, 13 cells in the diabetic pancreas and salivary ducts in Sjogren's syndrome (29). The presence of 'Y-IFN has been demonstrated at the site of inflammation (30).…”

Section: Discussionmentioning

confidence: 98%

“…Others in the field of organ transplantation have presented similar hypotheses concerning MHC antigen induction and allograft rejection (27). After studying HLA antigen expression in serial liver graft biopsy specimens, Gouw et al (28) have also hypothesized that the induction of MHC antigens on bile duct epithelium accelerates the alloresponse leading to rejection.…”

Section: Discussionmentioning

confidence: 99%

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Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

Saidman¹

1991

Hepatology

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

Saidman¹

1991

Hepatology

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“…In vivo, induced expression of MHC antigens has been reported for a number of other inflammatory sites, including transplanted kidneys (27), biliary epithelium in PBC (4), thyroid epithelium in Graves' disease, β cells in the diabetic pancreas and salivary ducts in Sjögren's syndrome (29). The presence of γ-IFN has been demonstrated at the site of inflammation (30).…”

Section: Discussionmentioning

confidence: 99%

Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

et al. 1991

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We have developed an in vitro system to study the interactions between biliary epithelium and lymphocytes using cultured human biliary epithelial cells. No class II antigens were detected by immunoperoxidase staining of the normal biliary epithelial cells, but alloactivated lymphocyte culture supernatants were able to induce class II expression. The activity of the supernatants was blocked with an anti-γ-interferon monoclonal antibody. In addition, recombinant human γ-interferon alone induced the expression of class II antigens and increased the intensity of class I staining of cultured biliary epithelial cells. Biliary epithelial cell-induced proliferation of alloreactive T lymphocytes demonstrated that the major histocompatibility complex molecules carry functional lymphocyte-activating determinants. The recognition of major histocompatibility complex determinants was confirmed by monoclonal antibody-blocking studies and by stimulation of an alloreactive T-cell clone. However, the biliary epithelial cells were much less potent stimulators than arterial endothelial cells tested in the same assay system.The biliary epithelium is a major target of lymphocytic attack in human liver allograft rejection and in many immunologically mediated liver diseases such as PBC (1,2). The immune damage in these disorders is thought to be mediated primarily by T cells. Major histocompatibility complex (MHC) antigens are likely the target of lymphocytic attack in rejection (3), and, although the target antigens in PBC have not yet been identified, the aberrant expression of class II antigens seen on the bile ducts in PBC livers has been hypothesized to playa role in the disease (4).The biliary epithelium in normal livers expresses class I but not class II human leukocyte antigens (HLA) (5-7). However, all three class II subregion products, namely HLA-DR, HLA-DP and HLA-DQ, have been detected on bile ducts in transplanted livers during rejection and other complications (5,8), in hepatic graft vs. host disease after bone marrow transplantation (9) and in PBC (4). It has been hypothesized that this expression is induced by soluble inflammatory mediators released from the invading mononuclear cells. Although the pathogenic role of this aberrant class II expression is unclear, we have previously shown that the increased destruction of bile duct epithelium during rejection is associated with HLA class II-specific lymphocytes invading the allograft (10). NIH Public Access Author ManuscriptHepatology. Author manuscript; available in PMC 2010 November 4. Published in final edited form as:Hepatology. 1991 February ; 13(2): 239-246. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptWe have established an in vitro model system to study the interactions between biliary epithelium and lymphocytes using cultured normal human biliary epithelial cells (BEC). The cultured BEC have been used to investigate the cytokines responsible for the up-regulation of class II MHC antigens and whether these MHC molecules were fu...

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“…The predominance of activation markers such as CD25 and proliferation markers such as Ki-67 have been associated with rejection episodes (54) as have increases in CD8 ϩ and CD45RO ϩ cells (55) and CD103 expression in infiltrating CD8 ϩ T cells (56), but under closer scrutiny, particularly when evaluating repeated rejection episodes after therapy and viral infections, these markers may not be clinically reliable. The propensity of renal tubular epithelium to express HLA-DR when under immune insult has long been recognized as a means to identify immunologically active infiltrates (57). Indeed, this marker is regularly used to assess atypical infiltrates and is particularly useful in assessing lymphopenic rejections after depletional induction (38).…”

Section: What More Can the Biopsy Tell Us?mentioning

confidence: 99%

Beyond Histology

Mannon¹,

Kirk²

2006

Clinical Journal of the American Society of Nephrology

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Kidney biopsy is the gold standard procedure for the assessment of allograft dysfunction. The differential diagnosis for both acute and chronic dysfunction can encompass a number of different causes, and a biopsy frequently can suggest a specific cause. However, many of these causes are difficult to distinguish on morphologic basis alone, and the information that is obtained from a biopsy is limited with regard to functional and prognostic importance. Additional methods therefore are needed to guide the diagnosis and the treatment of allograft dysfunction, and numerous methods have been studied. Potential markers include protein and gene expression profiles in the peripheral blood, the urine, and the graft itself, all compartments that are relevant to the alloimmune response. Recent comprehensive sequencing of the human genome has led to an unprecedented opportunity to develop these genetic and proteomic techniques, and ongoing evaluations of potential tests have led to an improved understanding of the complexity of immune responses. The future challenge for promising tests is validation in larger patient populations to facilitate their addition to the diagnostic armamentarium.

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Increased Expression of Hla-DR Antigens on Renal Tubular Cells in Renal Transplants: Relevance to the Rejection Response

Cited by 178 publications

References 28 publications

Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes

Beyond Histology

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