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Transplantation. 1998 Aug 15;66(3):339-49.

A role for persisting antigen, antigen presentation, and ICAM-1 in increased renal graft survival after oral or portal vein donor-specific immunization.

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  • 1Transplant Research Division, The Toronto Hospital, Ontario, Canada.

Abstract

BACKGROUND:

We studied the mechanism behind increased renal allotransplant survival when C3H mice received donor-specific portal vein or oral immunization with C57BL/6 cells. Both regimens lead to donor-specific increased graft survival, in association with decreased production of cytotoxic T lymphocytes and altered cytokine production from host lymphocytes (decreased interleukin [IL]-2 production; increased IL-4, IL-10, and transforming growth factor-beta).

METHODS:

We examined a role for persistent donor-derived antigen, in association with host dendritic cells, as well as a role for intercellular adhesion molecule-1 (ICAM-1), in the maintenance of unresponsiveness in host C3H spleen cells to donor antigen. We investigated whether there was a cooperative interaction between donor dendritic cells (DC) and host hepatic mononuclear cells in the induction of immunoregulation in C3H cells.

RESULTS:

In mice with surviving renal grafts, donor antigen, in association with host DC, induced the recall of cytotoxicity from C57BL/6 immune C3H spleen cells and IL-4 but not IL-2 production, despite the decreased cytotoxicity seen in the renal transplant recipients themselves. Fresh donor DC induced IL-2 but not IL-4 production. Blocking expression of ICAM-1 on donor grafts, either with anti-ICAM-1 monoclonal antibodies after renal grafting or using grafts from ICAM-1 "knockout" mice, led to further increased survival. Cultured C3H responder spleen cells, incubated with C57BL/6 DC and C3H hepatic cells, transferred hyporesponsiveness to C57BL/6 cells in vitro and in vivo (as assayed by survival of C57BL/6 renal allografts).

CONCLUSIONS:

Our data suggest a role for ICAM-1, persistent donor antigen (on host DC), and accessory hepatic monocytes in the induction and maintenance of tolerance after portal vein immunization.

PMID:
9721803
[PubMed - indexed for MEDLINE]
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