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Title: Early accumulation of interferon-gamma in grafts tolerized by donor-specific blood transfusion: friend or enemy?
Authors: Kitade, Hiroaki ×
Kawai, Masaru
Koshiba, Takaaki
Giulietti, Annapaula
Overbergh, Lutgart
Rutgeerts, Omer
Valckx, Dirk
Waer, Mark
Mathieu, Chantal
Pirenne, Jacques #
Issue Date: 27-Dec-2004
Series Title: Transplantation vol:78 issue:12 pages:1747-55
Abstract: BACKGROUND: We previously documented an early (day-2) interferon (IFN)-gamma accumulation in cardiac allografts of rats made tolerant by donor-specific blood transfusion (DSBT) but not in rejecting controls. This contrasted with the IFN-gamma peak seen later (day 5) in rejecting but not in tolerant rats. METHODS: To further examine the role of early intragraft IFN-gamma in DSBT-induced tolerance, we studied whether IFN-gamma up-regulation correlates with the magnitude of the DSBT effect and how IFN-gamma is influenced by interventions abrogating tolerance. RESULTS: The protective effect of DSBT depended upon the timing of administration: day-12 DSBT induced indefinite graft survival; day-6 DSBT gave a moderate, and day-0 DSBT, no graft prolongation. IFN-gamma up-regulation correlated with the DSBT effect: it was maximal after day-12 DSBT, intermediate after day-6 DSBT, and absent after day-0 DSBT. Tolerant splenocytes transferred tolerance into naive rats in a donor-specific manner, indicating that alloantigen-specific regulatory cells operate. Thymectomy prevented regulatory cells development, caused further amplification of intragraft IFN-gamma, and led to rejection, although graft survival was still prolonged. CONCLUSIONS: Day 2 intragraft IFN-gamma correlates with the DSBT protective effect. Thymectomy abrogates DSBT-induced tolerance, prevents regulatory cell development, and paradoxically causes further accumulation of intragraft IFN-gamma. These data indicate that DSBT has a stimulatory and a (thymus-dependent) inhibitory effect on early intragraft IFN-gamma. Intragraft IFN-gamma is beneficial, providing it occurs early and remains moderate. The role of intragraft IFN-gamma in tolerance and rejection depends upon the timing and the degree of production and perhaps the type of IFN-gamma producing cells (regulatory or effector).
URI: 
ISSN: 0041-1337
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Abdominal Transplantation
Research Group Experimental Neurology
Clinical and Experimental Endocrinology
Laboratory of Nephrology
Laboratory of Experimental Transplantation
× corresponding author
# (joint) last author

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