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

Abstract

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.

Overexpression of Interleukin-13 Induces Minimal-Change–Like Nephropathy in Rats

“…Previous studies have shown that IL-13 in combination with IL-1␣ and IFN-␥ could induce B7-1 expression on human proximal tubular epithelial cells (45). In this experiment, we demonstrated increased glomerular IL-4R␣ and IL-13R␣2 gene expression, as well as increased protein expression of IL-4R␣, localized to the podocytes in most of the glomeruli of nephrotic rats, suggesting that IL-13 may act directly on podocytes.…”

Characterization of renal interstitial fibroblast-specific protein 1/S100A4-positive cells in healthy and inflamed rodent kidneys

“…Indeed, a variety of functions has been attributed to this protein (Barraclough 1998;Mazzucchelli 2002;Taylor et al 2002). Moreover, in inflammatory environments, tubular cells can up-regulate a variety of proteins that are normally found in cells of the immune system, for instance, MHC class II (Takei et al 2000), B7 (Niemann-Masanek et al 2002), CD14 (Fearns et al 1995;Morrissey et al 2000), CD44 (Wuthrich 1992) and CD40 (Hong et al 2002;van Kooten et al 2000). Also, cytoskeletal proteins, such as vimentin, may be up-regulated in regenerating renal epithelial cells (Witzgall et al 1994;Zhu et al 1996).…”

Cellular pathophysiology of ischemic acute kidney injury

“…CD40 ligation also induces RANTES production by human renal tubular epithelia, an effect that is amplified by production of IL-4 and IL-13 by Th2 cells, a subpopulation of T cells (42). Ischemia/reperfusion increases expression of B7-1 and B7-2, costimulatory tubule cell molecules that interact with CD28 on T lymphocytes and facilitate cytokine production (43).…”