Lymphocyte adhesion molecules in T cell-mediated lysis of human kidney cells

Suranyi, Michael; Bishop, Alex; Clayberger, Carol; Krensky, Alan M.; Leenaerts, Peter L.; Aversa, Gregorio; Hall, Bruce M.

doi:10.1038/ki.1991.39

Cited by 43 publications

(15 citation statements)

References 25 publications

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“…Although the increased interstitial ICAM-1 is strategically crucial for recruiting inflammatory cells to the interstitium, how an overexpression of ICAM-1 by tubular cells, that is limited to their apical aspects, interacts with interstitial inflammatory cells remains unknown. On the other hand, this distinctive topography of ICAM-1 expression, confirmed in every human or experimental study that documents tubular ICAM-1 upregulation, may facilitate migration of inflammatory cells into tubular epithelial layer and mediate the various tubular cell-inflammatory cell interactions, including cell-mediated cytotoxicity [4, 15, 25, 26, 27, 28]. …”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, altered expression of integrins and the immunoglobulin molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on parenchymal cells may contribute to cytotoxic interactions with infiltrating inflammatory cells [4, 5]. Altered expression of ICAM-1 and VCAM-1 in glomerular, tubulointerstitial, and vascular compartments has been reported in a variety of human kidney diseases and in experimental animal models of renal disease [2, 3, 6, 7, 8].…”

Section: Introductionmentioning

confidence: 99%

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Expression of Adhesion Molecules in Kidney with Experimental Chronic Obstructive Uropathy: The Pathogenic Role of ICAM-1 and VCAM-1

Shappell

Mendoza

Gurpinar³

et al. 2000

Nephron

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Background: Chronic obstructive uropathy induced by maintained unilateral ureter ligation in the rat is characterized morphologically by interstitial inflammation, interstitial fibrosis, and tubular atrophy. Infiltrating mononuclear inflammatory cells, particularly T lymphocytes and macrophages, may contribute to the progression of this lesion by mediating tubular injury and by the activation of interstitial fibroblasts, with resultant tubular atrophy and interstitial fibrosis, respectively. Altered expression and activation of adhesion molecules by leukocytes, vascular endothelial cells, and parenchymal cells likely contributes both to the infiltration of inflammatory cells into the tubulointerstitial compartment and to the interaction of activated inflammatory cells with parenchymal cells. Methods: In the current study, we examined changes in the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in a 90-day model of maintained unilateral ureter ligation in male Sprague-Dawley rats. Results: Rat kidneys showed constitutive expression of ICAM-1 mRNA and constitutive immunostaining for ICAM-1 in peritubular capillaries, glomeruli, and a small percentage of cortical tubules. Ureter ligation resulted in a rapid increase in ICAM-1 mRNA, which was almost 2-fold greater than those of the contralateral and control kidneys as early as 3 h and which was maintained at a 4- to 6-fold higher level in the ligated vs. contralateral kidneys throughout the entire 90-day time course. There was a marked increase in ICAM-1 immunostaining within the tubular epithelium, with up to 80% of both cortical and medullary tubular cross-sections showing strong apical immunostaining from day 6 to 25, with a subsequent decrease throughout the remainder of the experiment. ICAM-1 immunostaining in the expanding interstitium in the ligated kidneys showed a gradual increase throughout the duration of the experiment. In contrast, glomerular immunostaining for ICAM-1 was decreased in the ligated compared to the contralateral kidneys throughout the entire experiment. There was a later but prominent increase in VCAM-1 mRNA in ligated kidneys, which was first evident at 2 days and which was maintained 2- to 10-fold greater than the contralateral kidneys throughout the entire time course. VCAM-1 immunostaining increased in the expanding interstitium, but decreased in glomeruli in obstructed vs. contralateral kidneys. Tubular staining for VCAM-1 did not change after ureter ligation. Conclusion: Increased ICAM-1 and VCAM-1 may contribute to the prominent inflammatory cell infiltration in the chronic tubulointerstitial nephritis accompanying maintained unilateral ligation. Tubule expression of ICAM-1, which occurs during a similar time course as previously documented for tubular cell proliferation and especially tubular cell apoptosis in this model, may contribute to injurious interactions of activated inflammatory cells with tubular epithelium.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Adhesion Molecules in Kidney with Experimental Chronic Obstructive Uropathy: The Pathogenic Role of ICAM-1 and VCAM-1

Shappell

Mendoza

Gurpinar³

et al. 2000

Nephron

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“…However, the factors that induce B7-H1 expressionin vivo were not clarified at present. Previous data have revealed that under inflammatory conditions, the release of proinflammatory cytokines such as TNF-α, IFN-γ, MCP-1 or RANTES was induced by TECs, and those proinflammatory factors could induce or augment the expression of a range of molecules such as MHC-II antigen [27], ICAM-1 [28], VCAM-1 and LFA-3 [29, 30]. Here we also found B7-H1 was induced to express on TECs by the stimulation of some inflammatory factors such as IL-1α, TNF-α or IFN-γ in vitro.…”

Section: Discussionmentioning

confidence: 99%

Expression of B7-H1 in Inflammatory Renal Tubular Epithelial Cells

Chen

Zhang

et al. 2005

Nephron Exp Nephrol

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Background: Renal tubular epithelial cells (TECs) function as antigen-presenting cells (APCs) as they constitutively express MHC-II molecules and have the capacity to present peptide antigen to T cells. Nevertheless, co-stimulatory signals provided by TECs for regulating T cell activation have not been fully characterized. We therefore investigated the expression of B7-H1, a member of the B7 superfamily, on TECs under normal or pathologic conditions in vivo and analyzed the regulation and functional role of it after proinflammatory factors treatment in vitro. Methods: Immunohistological staining for B7-H1 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Furthermore, we also detected B7-H1 protein expression on cultured human TECs stimulated by various inflammatory factors and performed TEC/T-cell co-cultured experiment to determine TEC-associated B7-H1 in regulating CD4⁺ T cell activation as well as antigen presentation. Results: Significant B7-H1 protein was detected in TECs of diseased renal samples. Although the presence of B7-H1 does not have any correlation with clinicopathological variables, marked B7-H1 expression on sections without interstitial inflammation revealed that B7-H1 has some protective function. In vitro, the expression of B7-H1 on TECs was increased after TECs were stimulated with IL-1α, LPS, TNF-α, IFN-γ or anti-CD40. Co-cultured experiments revealed that TEC-related B7-H1 was identified as a strong inhibitor of CD4⁺ T-cell activation as assessed by increased cytokine production (interleukin-2 and interferon-γ) and expression levels of the T cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (clone MIH1). Interestingly, IL-2 production by C10 T cells after antigen presentation by murine TECs was also enhanced when the B7-H1/PD-1 pathway was interrupted. Conclusion: This study clearly shows that B7-H1 is an inducible renal tubular epithelial antigen that inhibits T cell activation. It is speculated that B7-H1/PD-1 pathway might play a role in protecting tubular epithelium from immune-mediated damage and active delivery of the B7-H1 inhibitory signal represents a novel therapeutic strategy in autoimmune renal diseases.

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“…Cultured PTEC produce proinflammatory cytokines such as TNFα, MCP-1 and RANTES that can induce or augment the expression of a range of molecules which regulate cellular immunogenicity. These include class I and II MHC antigens [17]and the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) [24, 25], vascular cell adhesion molecule-1 (VCAM-1) [26]and lymphocyte function associated antigen-3 (LFA-3) [27]. This shows that PTEC express several cytokines, costimulatory and adhesion molecules under inflammatory conditions leading to the progression of renal diseases.…”

Section: Introductionmentioning

confidence: 99%

B7-1 (CD80) and B7-2 (CD 86) Expression in Human Tubular Epithelial Cells in vivo and in vitro<footref rid="foot01"><sup>1</sup></footref>

Niemann-Masanek

Mueller

Yard

et al. 2002

Nephron

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Background: Tubulointerstitial inflammation with infiltration of mononuclear cells plays an important role in acute allograft rejection and in the progression of renal diseases. We therefore investigated in vivo the expression of the costimulatory molecules B7-1 and B7-2 on proximal tubular epithelial cells (PTEC) under normal and pathologic conditions and analyzed the regulation and functional role of these molecules after cytokine and CD40 activation in vitro. Methods: Immunohistological staining for B7-1 and B7-2 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Patients were divided into three groups: group A: diffuse interstitial inflammation; group B: minor interstitial inflammation; group C: no interstitial inflammation. In addition, the expression of B7-1 and B7-2 protein and mRNA of cultured PTEC that had been stimulated with cytokine-combinations in absence or presence of a stimulatory anti-CD40 antibody was investigated by means of FACS analysis and RT-PCR. The functional role was analyzed in MKLCs with cytokine and anti-CD40 prestimulated PTEC by measuring IFN-γ and IL-2 expression in absence or presence of CTLA4-Ig by ELISA. Results: Group A patients showed intense tubular staining for B7-1 and B7-2, group B patients showed mild staining, whereas in group C patients B7-1 and B7-2 staining was negative or only weakly positive. In vitro, the presence of B7-1 and B7-2 on PTEC was increased after stimulation with combinations of IL-1α, IL-4, IFN-γ or IL-13 instead of IL-4 and CD40 activation. B7-1 and B7-2 mRNA could be detected in PTEC as well. In MKLCs only cytokine and anti-CD40 prestimulated PTEC were able to stimulate IFN-γ and IL-2 production by purified T cells, which could be blocked dose-dependently by CTLA4-Ig. Conclusion: This study clearly shows that B7-1 and B7-2 can be induced on PTEC in vivo and in vitro. After B7-1 and B7-2 induction, PTEC costimulate CD28 on T lymphocytes resulting in cytokine production. This might be of relevance in allograft rejection and in various kidney diseases.

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Lymphocyte adhesion molecules in T cell-mediated lysis of human kidney cells

Cited by 43 publications

References 25 publications

Expression of Adhesion Molecules in Kidney with Experimental Chronic Obstructive Uropathy: The Pathogenic Role of ICAM-1 and VCAM-1

Expression of Adhesion Molecules in Kidney with Experimental Chronic Obstructive Uropathy: The Pathogenic Role of ICAM-1 and VCAM-1

Expression of B7-H1 in Inflammatory Renal Tubular Epithelial Cells

B7-1 (CD80) and B7-2 (CD 86) Expression in Human Tubular Epithelial Cells in vivo and in vitro<footref rid="foot01"><sup>1</sup></footref>

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