Tr1 cell immunotherapy promotes transplant tolerance via de novo Tr1 cell induction in mice and is safe and effective during acute viral infection.
Tr1 cell therapy is considered an emerging approach to improve transplant tolerance and enhance allogeneic graft survival. However, it remains unclear how Tr1 cells promote transplant tolerance and whether they will be safe and stable in the face of an acute viral infection. By employing a mouse model of pancreatic islet transplantation, we report that Tr1 cell therapy promoted transplant tolerance via de novo induction of Tr1 cells in the recipients. Acute viral infection with lymphocytic choriomeningitis virus (LCMV) had no impact on Tr1 cell number and function, neither on the Tr1 cells infused nor on the ones induced, and that was reflected in the robust maintenance of the graft. Moreover, Tr1 cell immunotherapy had no detrimental effect on CD8 and CD4 anti-LCMV effector T-cell responses and viral control. Together, these data suggest that Tr1 cells did not convert to effector cells during acute infection with LCMV, maintained transplant tolerance and did not inhibit antiviral immunity.
['Jofra|Tatiana|T|', 'Di Fonte|Roberta|R|', 'Galvani|Giuseppe|G|', 'Kuka|Mirela|M|', 'Iannacone|Matteo|M|', 'Battaglia|Manuela|M|', 'Fousteri|Georgia|G|0000-0001-7745-7517']
D000818:Animals D018414:CD8-Positive T-Lymphocytes D003922:Diabetes Mellitus, Type 1 D007108:Immune Tolerance D016219:Immunotherapy, Adoptive D007515:Islets of Langerhans D016381:Islets of Langerhans Transplantation D008216:Lymphocytic Choriomeningitis D008217:Lymphocytic choriomeningitis virus D051379:Mice D008807:Mice, Inbred BALB C D008810:Mice, Inbred C57BL D023421:Models, Animal D050378:T-Lymphocytes, Regulatory
Transplant tolerance Pancreatic islet transplantation Lymphocytic choriomeningitis virus (LCMV) Type 1 diabetes (T1D) Type 1 regulatory cells (Tr1)