Transplant immunology
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Transplant immunology · Jun 1995
Cytokine gene expression in rejecting and tolerant rat lung allograft models: analysis by RT-PCR.
Cytokine gene expression is a critical component of the lung allograft rejection (AR) response and tolerance development in rat models. In order to determine the specificity of cytokine gene expression for AR and tolerance, we examined cytokine (interleukin-2) (IL-2), (gamma-interferon) (gamma-IFN), IL-4, IL-10 and tumor necrosis factor-alpha (TNF-alpha) and control (cyclophilin) mRNA levels in two models of rat lung allograft rejection by RT-PCR (reverse transcriptase polymerase chain reaction), Southern blotting. The first model (WKY-->F344) develops a mild to moderate lymphocytic infiltrate on days 14-21 post-transplant (stage II-III AR), which spontaneously resolves by day 35 post-transplant with subsequent development of allograft tolerance (grafts surviving without evidence of AR for > 140 days). Conversely, F344-->WKY develops a similar lymphocytic infiltrate by day 14 post-transplant, but by day 21 post-transplant the graft shows severe AR (stage III-IV) and has haemorrhagic infarction with alveolar haemorrhage. ⋯ 1) The WKY-->F344 tolerance model develops mild to moderate lymphocytic infiltrates on day 14 which is associated with low level IL-2, gamma-IFN and TNF-alpha gene expression. IL-10 and IL-4 are present at day 3; however, by day 14, IL-10 is the predominantly expressed Th2 cytokine and IL-4 is not expressed. The infiltrates ultimately resolve and the animals develop a functional tolerance to their grafts.4