Interferon-gamma-treated renal tubular epithelial cells induce allospecific tolerance

Details

Serval ID
serval:BIB_C70918E6EBF6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interferon-gamma-treated renal tubular epithelial cells induce allospecific tolerance
Journal
Kidney International
Author(s)
Frasca  L., Marelli-Berg  F., Imami  N., Potolicchio  I., Carmichael  P., Lombardi  G., Lechler  R.
ISSN
0085-2538 (Print)
Publication state
Published
Issued date
03/1998
Volume
53
Number
3
Pages
679-89
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Abstract
Following organ transplantation, tissue parenchymal cells commonly express major histocompatibility complex (MHC) class II molecules as a result of local cytokine release, and thus acquire the capacity to present donor MHC alloantigens to alloreactive CD4+ T cells. The consequences of such a presentation are likely to be relevant in the induction of tolerance to the transplanted tissues, and this has been reported in animal models of transplantation and in humans. In this study, the consequences of antigen presentation by interferon-gamma (IFN-gamma)-treated human renal tubular epithelial cells (RTEC) to resting and activated CD4+ T cells were investigated. Allogeneic RTEC were unable to stimulate proliferation by peripheral blood CD45 RA+ or RO+ CD4+ T cells from three HLA-mismatched responders. The response to RTEC was partially reconstituted by the addition of murine L cell transfectants expressing human B7.1 (DAP.3-B7), suggesting that the failure of RTEC to stimulate a primary alloresponse was due, at least in part, to a lack of costimulation. T cell clones dependent on B7-mediated co-stimulation also did not respond to peptide presented by RTEC. Most importantly, this lack of reactivity was accompanied by the induction of nonresponsiveness. Incubation with allogeneic, DR-expressing RTEC induced allospecific hyporesponsiveness in both CD45RA+ and RO+ cells. Similarly, overnight incubation with antigen-pulsed RTEC induced nonresponsiveness in the B7-dependent T cell clones. These results suggest that MHC class II expression on RTEC may contribute to the induction of an allospecific nonresponsiveness following organ transplantation.
Keywords
Animals Antigen Presentation Antigens, CD45/metabolism Antigens, CD80/genetics CD4-Positive T-Lymphocytes/immunology Cell Line Epithelial Cells/drug effects/immunology Histocompatibility Antigens Class II/metabolism Humans Immune Tolerance/*drug effects Interferon Type II/*pharmacology Isoantigens/metabolism Kidney Tubules/cytology/*drug effects/*immunology L Cells (Cell Line) Mice Transfection Transplantation Immunology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 15:16
Last modification date
20/08/2019 15:42
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