1. IL-10 Induces T Cell Exhaustion During Transplantation of Virus Infected Hearts.
- Author
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Gassa, Asmae, Fu Jian, Kalkavan, Halime, Duhan, Vikas, Honke, Nadine, Shaabani, Namir, Friedrich, Sarah-Kim, Dolff, Sebastian, Wahlersg, Thorsten, Kribben, Andreas, Hardt, Cornelia, Lang, Philipp A., Witzke, Oliver, and Lang, Karl S.
- Subjects
HEART transplantation ,VIRUS disease transmission ,LYMPHOCYTIC choriomeningitis virus ,INTERLEUKIN-10 ,PATHOGENIC viruses ,T cells ,IMMUNE response - Abstract
Background/Aims: Unexpected transmissions of viral pathogens during solid organ transplantation (SOT) can result in severe, life-threatening diseases in transplant recipients. Immune activation contributes to disease onset. However mechanisms balancing the immune response against transmitted viral infection through organ transplantation remain unknown. Methods & Results: Here we found, using lymphocytic choriomeningitis virus (LCMV), that transplantation of LCMV infected hearts led to exhaustion of virus specific CD8+ T cells, viral persistence in organs and survival of graft and recipient. Genetic depletion of Interleukin-10 (IL-10) resulted in strong immune activation, graft dysfunction and death of mice, suggesting that IL-10 was a major regulator of CD8+ T cell exhaustion during SOT. In the presence of memory CD8+ T cells, virus could be controlled. However sufficient antiviral immune response resulted in acute rejection of transplanted heart. Conclusion: We found that virus transmitted via SOT could not be controlled by naïve mice recipients due to IL-10 mediated CD8+ T cell exhaustion which thereby prevented immunopathology and graft failure whereas memory mice recipients were able to control the virus and induced graft failure. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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