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Title: Role of CD4+ and CD8+ T cells in the rejection of heart or islet xenografts in recipients with xenotolerance in the innate immune compartment
Authors: Devos, Timothy
Yan, Yan
Segers, Constant
Rutgeerts, Omer
Laureys, Jozef
Gysemans, Conny
Mathieu, Chantal
Waer, Mark # ×
Issue Date: Jan-2005
Publisher: Appleton & Lange
Series Title: Transplantation Proceedings vol:37 issue:1 pages:516-517
Abstract: To further study the interactions between innate and adaptive immunity in xenotransplantation, we explored the relative contribution of T-cell subsets in vascularized (heart) and cellular (islets) xenografts in a model with established xeno-non-reactivity of the innate system. MATERIALS: Specific innate xenotolerance was induced in xenoheart (hamster) recipients (nude rats) by a tolerizing regimen (TR), consisting of donor antigen infusion, temporary natural killer (NK)-cell depletion and a 4-week administration of leflunomide. Hamster pancreatic islets were transplanted either 1 week after heart transplantation or alone and syngeneic T-cell adoptive transfer was performed 10 days later. Purified CD3(+), CD4(+), and CD8(+) T cells were given 2 weeks after withdrawal of all drugs. At the day of rejection, xenografts were removed for histology. Serum was taken and IgM and IgG xenoantibody titers were measured by flow cytometry. RESULTS: Both heart and islet grafts were rejected after CD4(+) reconstitution. After CD8(+) T-cell adoptive transfer, cellular grafts were not rejected but vascularized grafts were rejected, although only after several months. Rejection in CD4(+) reconstituted nude rats was accompanied by the generation of predominantly IgG xenoantibodies. CONCLUSION: CD4(+) T lymphocytes are able to rapidly initiate the rejection of islet xenografts in the presence of a xenotolerant innate immune system either by breaking the "innate tolerance" (e.g., by activating macrophages and NK-cells) or through a mechanism without any involvement of the innate tolerance (e.g., T-dependent IgG antibody production). In contrast, CD8(+) T cells provoke a late rejection of only xenoheart grafts.
URI: 
ISSN: 0041-1345
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Laboratory of Nephrology
Laboratory of Experimental Transplantation
× corresponding author
# (joint) last author

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