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Increased intragraft IL-15 mRNA expression after liver transplantation
C C Baan1, H G Niesters, H J Metselaar
1Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands. baan@inw1.azr.nl
Abstract:
To study T-cell/macrophage interactions at the molecular level in clinical allograft rejection, we measured intragraft mRNA expression of the T-cell derived cytokine IL-2 and the macrophage derived chemokine IL-15, a novel cytokine associated with T-cell activation, in post-transplant liver biopsies (n = 33) and in non-transplanted control liver tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed biopsies without evidence of rejection (n = 12), with spontaneously resolving histological rejection (n = 10), or with histological rejection accompanied with clinical rejection (n = 11) defined by rising serum bilirubin and aspartate amino transaminase levels. IL-15 mRNA expression was present in the majority of post-transplant liver biopsies (91%, 30/33) and was significantly upregulated as compared with non-transplanted liver tissue (p = 0.005). However, the increased intragraft IL-15 mRNA level was not indicative for rejection. In contrast to intragraft IL-15 mRNA expression, IL-2 mRNA transcription was measured in the minority of the post-transplant liver biopsies (15%, 5/33) and not detectable in control specimens. In addition, IL-2 mRNA was almost specifically measured in rejection biopsies concurrent with graft dysfunction (36%, 4/11 versus 1/22 without clinical rejection; p = 0.03). No relation between intragraft IL-2 and IL-15 mRNA expression was found. The IL-15 mRNA expression levels were not higher in the IL-2 negative rejections compared with those in IL-2 positive rejections. To conclude, in contrast to IL-2, the function of IL-15 in T-cell mediated rejection remains unclear. The overall high IL-15 mRNA levels in sites of immune responses suggests that the macrophage-derived mediator IL-15 is involved in a constant flow of T-cells from the circulation into the graft.
Insights
Interleukin-15 (IL-15) mRNA is upregulated in liver transplants but not indicative of rejection. Interleukin-2 (IL-2) mRNA is a specific marker for clinical allograft rejection and graft dysfunction.
Area of Science:
- Immunology
- Transplantation Biology
- Molecular Medicine
Background:
- Clinical allograft rejection involves complex T-cell and macrophage interactions.
- Understanding molecular mediators is crucial for diagnosing and managing rejection.
- Cytokines like IL-2 and IL-15 play roles in immune responses and T-cell activation.
Purpose of the Study:
- To investigate the role of IL-2 and IL-15 mRNA expression in liver allograft rejection.
- To differentiate the expression patterns of IL-2 and IL-15 in various rejection states.
- To assess the potential of these cytokines as biomarkers for clinical rejection.
Main Methods:
- Analysis of intragraft mRNA expression of IL-2 and IL-15 using RT-PCR.
- Study included post-transplant liver biopsies (n=33) and control liver tissue.
- Biopsies were categorized into no rejection, resolving rejection, and clinical rejection groups.
Main Results:
- IL-15 mRNA was significantly upregulated in most post-transplant biopsies compared to controls, but not specific for rejection.
- IL-2 mRNA was detected in a minority of biopsies, primarily in those with clinical rejection and graft dysfunction (p=0.03).
- No correlation was found between IL-2 and IL-15 mRNA levels; IL-15 levels were similar in IL-2 positive and negative rejections.
Conclusions:
- IL-2 mRNA expression is a potential indicator of T-cell mediated rejection and graft dysfunction in liver allografts.
- The role of IL-15 in T-cell mediated rejection remains unclear, despite its upregulation.
- High IL-15 levels suggest a role in T-cell recruitment to the graft, independent of active rejection.