Abstract
BackgroundCMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation.MethodsWe prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4+ and CD8+ T-cells, T-regs (CD4+CD25+FoxP3+) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10).ResultsHigher initial CMV-specific CD4+ T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4+ T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4+ T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes.ConclusionsThis study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4+ T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.
Highlights
After solid organ transplantation, cytomegalovirus (CMV)replication may result in viral syndrome or tissue invasive disease [1]
A total of 30 patients were enrolled including 20 patients with high-level viremia and/or symptomatic CMV-disease who required the commencement of anti-viral therapy
This group was compared to 10 patients with asymptomatic low-level viremia, who spontaneously cleared CMV viremia without treatment
Summary
Cytomegalovirus (CMV)replication may result in viral syndrome or tissue invasive disease [1]. In the post-transplant setting the adaptive immune response, and CD4+ and CD8+ T-cell responses play a prominent role in the control of CMV replication. A decrease in CMV-specific CD4+ and CD8+ T-cells has been associated with progressive CMV-replication [3,4,5,6,7,8]. Internal regulatory mechanisms such as regulatory T-cells (T-regs; CD4+CD25+FoxP3+) may modify CMV-specific CD4+ and CD8+ T-cell functions leading to an increased risk for progressive CMV-replication [10]. T-regs play an important role in maintaining self-tolerance and are being studied as a potential means to promote an immunotolerant state post-transplant [11]. CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. We explored T-regs and Th-17 frequencies during CMVreplication after transplantation
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