EXPRESSION OF HLA ANTIGENS ON RENAL TUBULAR CELLS IN CULTURE
- 1 December 1986
- journal article
- research article
- Published by Wolters Kluwer Health in Transplantation
- Vol. 42 (6), 671-678
- https://doi.org/10.1097/00007890-198612000-00018
Abstract
The altered expression of HLA antigens on tissues during rejection is of potential importance to both the initiation and effector arms of the alloimmune response. Associated with rejection episodes, renal tubular cell expression of HLA DR (class II) antigens has been observed to be markedly increased. In this study an in vitro assay using cultured renal tubular cells from normal human kidneys was developed. Monoclonal antibodies to detect HLA DR and HLA A, B, C (class I) molecules were used to identify these antigens on cultured tubular cells either by indirect immunofluorescence stains and flow cytometric analysis or by immunoperoxidase stains with cytological analysis. With these techniques normal cultured cells had little membrane or cytoplasmic HLA DR but did have membrane HLA A, B, C. Culture of renal tubular cells with either snpernatants from mixed lymphocyte cultures or purified gamma interferon induced expression of HLA DR, with maximum expression occnring between day 4 and day 6. Increased HLA A, B, C expression was also observed. This increased expression of HLA antigens was shown not to be dependent upon increased cell division of the cultured cells, and removal of gamma interferon from the cultures resulted in a decay in both HLA DR and A, B, C expression within days. HLA expression was inhibited by addition of protein synthesis inhibitor cycloheximide, but not by the addition of puromycin, mitomycin C, or actinomycin D—which suggested that tubular cells had transcribed m RNA for both HLA DR and A, B, C antigens. Expression of HLA antigens was not inhibited by cyclosporine, corticosteroids, or azathioprine. These studies demonstrate that the increased expression of HLA antigens seen in renal allografts at the time of rejection episodes can be explained by the release of lymphokines, especially gamma interferon, by infiltrating cells, and that reduced HLA DR expression of transplanted kidneys in patients treated with cyclosporine is not due to the drug directly inhibiting HLA expression by graft cells.This publication has 4 references indexed in Scilit:
- Massive induction of donor-type class I and class II major histocompatibility complex antigens in rejecting cardiac allografts in the rat.The Journal of Experimental Medicine, 1985
- Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon.The Journal of Experimental Medicine, 1983
- Regulation of murine macrophage Ia antigen expression by a lymphokine with immune interferon activity.The Journal of Experimental Medicine, 1982
- The immunohistochemical demonstration of major histocompatibility antigens in the human kidney using monoclonal antibodiesPathology, 1982