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Title: Paradoxical early upregulation of intragraft Th1 cytokines is associated with graft acceptance following donor-specific blood transfusion
Authors: Koshiba, Takaaki ×
Giulietti, Annapaula
Van Damme, Boudewijn
Overbergh, Lutgart
Rutgeerts, Omer
Kitade, Hiroaki
Waer, Mark
Mathieu, Chantal
Pirenne, Jacques #
Issue Date: Mar-2003
Publisher: Springer International
Series Title: Transplant International vol:16 issue:3 pages:179-85
Abstract: Donor-specific blood transfusion (DSBT) promotes graft acceptance in certain experimental and clinical situations. However, the exact nature of the operating mechanisms, and in particular the role of Th1/Th2 cytokines, remains controversial. We recently described a fully mismatched rat combination [RA rat (RT1p) to PVG rat (RT1c)] in which a single pre-transplant (Tx) DSBT induces donor-specific tolerance following heart transplantation (Htx). In order to delineate better the role of Th1 and Th2 cytokines in the development of tolerance versus rejection, we studied the intragraft mRNA for Th1 and Th2 cytokines at different time points post-Tx in rejecting and DSBT-tolerized heart grafts. We performed reverse transcriptase-polymerase chain reaction (RT-PCR) to examine intragraft Th1/Th2 cytokines profile. In contrast to findings from previous data, we detected an early (post-Tx day 2) Th1 cytokine upregulation. Th1 downregulation/Th2 immune deviation was observed only at a later period (post-Tx day 30). Consistent with this Th1 early upregulation, a dense mononuclear cellular infiltrate was seen in tolerized grafts, which was equivalent to that seen in rejecting grafts. Despite in vivo unresponsiveness, peripheral lymphocyte derived from tolerant animals proliferated against donor-matched antigens to the same degree as against those of a third party until post-Tx day 30. Altogether, these observations (dense graft cellular infiltrate, early post-Tx Th1 cytokine production, early preserved cellular proliferative responses), suggest that the development of tolerance is preceded by an active Th1 cytokine-mediated immune response. The mechanisms by which an early Th1 response promotes tolerance need to be further studied.
ISSN: 0934-0874
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Clinical and Experimental Endocrinology
Laboratory of Nephrology
Laboratory of Abdominal Transplantation
Research Group Experimental Neurology
Laboratory of Experimental Transplantation
× corresponding author
# (joint) last author

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