The form of allo-MHC class I antigen expressed by hepatocytes is critical in determining IL-2 responses by helper T cells

Graeb, Christian and Scherer, M. N. and Tange, S. and Jauch, Karl-Walter and Geissler, E. K. (1999) The form of allo-MHC class I antigen expressed by hepatocytes is critical in determining IL-2 responses by helper T cells. LANGENBECKS ARCHIVES OF SURGERY. pp. 235-239. ISSN 1435-2443,

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Abstract

Background: Evidence suggests that liver transplants have immunosuppressive effects. It has been proposed that since hepatocytes produce significant amounts of soluble MHC class I antigen, these molecules may have donor-specific immunosuppressive effects. Therefore, introduction of hepatocytes expressing donor-MHC antigen to potential organ recipients could promote subsequent allograft survival. To support this theory we have recently shown by in vivo gene transfer that soluble donor-MHC class I antigen can prolong liver allograft survival. Interestingly, we also have data that suggests one possible mechanism of this effect could relate to donor-soluble MHC antigen inhibition of helper T cell IL-2 production. Aim: Since liver transplantation involves introduction of hepatocytes that express relatively large amounts of membrane-bound donor MHC antigen, we performed experiments here to determine if this non-soluble form of the antigen also reduces IL-2 responses by helper T-cells. Methods: Lewis (RT1.A(1)) rats were injected with syngeneic hepatocytes transfected with plasmid DNA encoding the allogenic membrane-bound MHC class I antigen, RT 1.A(a). One day after injection, lymphocytes from spleen and lymph node were tested in mixed lymphocyte cultures for their IL-2 response against ACI (RT1.A(a)) stimulator cells. Results: In contrast to our previous findings, where soluble allo-MHC molecules suppressed the IL-2 response by helper T-cells, the membrane-bound form failed to decrease IL-2 production. Moreover, the membrane-bound alloantigen significantly stimulated an increase in IL-2 secretion. Conclusion: Our data suggests that although soluble forms of donor-MHC antigen may have immunosuppressive properties, exposure of potential organ transplant recipients to hepatocytes expressing membrane-bound forms of the same antigen may increase the risk for immunologic sensitization.

Item Type: Article
Uncontrolled Keywords: TRANSPLANTATION; IMMUNITY;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Nov 2022 09:46
Last Modified: 30 Nov 2022 09:46
URI: https://pred.uni-regensburg.de/id/eprint/48685

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