title: IL-10 Induces T Cell Exhaustion During Transplantation of Virus Infected Hearts.
abstract: OBJECTIVE
  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 &amp;
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Asmae
authors.initials: A
authors.lastname: Gassa
authors.forename: Fu
authors.initials: F
authors.lastname: Jian
authors.forename: Halime
authors.initials: H
authors.lastname: Kalkavan
authors.forename: Vikas
authors.initials: V
authors.lastname: Duhan
authors.forename: Nadine
authors.initials: N
authors.lastname: Honke
authors.forename: Namir
authors.initials: N
authors.lastname: Shaabani
authors.forename: Sarah-Kim
authors.initials: SK
authors.lastname: Friedrich
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dolff
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wahlers
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hardt
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control* / Q000821:virology; D006085:Graft Survival; D006321:Heart / Q000821:virology*; D016027:Heart Transplantation / Q000009:adverse effects*; D007114:Immunization; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10