Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

The interplay between transplant tolerance to pancreatic islets and acute anti-viral immune responses (#150)

Georgia Fousteri 1 , Tatiana Jofra 1 , Manuela Battaglia 1
  1. San Raffaele Scientific Institute, Milan, Italy

Viral infection presents a potent barrier to transplant tolerance induction. Understanding how viral infections alter transplant tolerance may lead to improved approaches to achieve life-long and safe organ engraftment. To determine whether acute viral infections modulate tolerance to islet allograft and vice versa, how immunosuppression affects anti-viral immunity, we used a murine model of allogeneic islet transplantation. In this setting, a specific immunomodulatory treatment leads to transplant tolerance mediated by both Foxp3+ Treg and Tr1 cells. We found that acute infection with lymphocytic choriomeningitis virus (LCMV) at the end of a 30-day treatment with G-CSF and the immunosuppressive drug rapamycin (G-CSF/RAPA) did not impinge transplant tolerance. Treg cell levels reduced at the peak of the antiviral response (i.e. 8 days after infection) but returned to basal numbers after the contraction phase (i.e. >15 days after infection). G-CSF/RAPA treatment did not prevent the generation of LCMV-specific cytotoxic lymphocytes (CTLs), but instead increased their differentiation toward memory cells. Since mTOR, the mammalian target of rapamycin, has immunostimulatory effects on the generation of memory CD8+ T cells, we conclude that G-CSF/RAPA treatment acted directly on antiviral CTLs through the mTOR molecular pathway. Thus these findings propose that cell-intrinsic mechanisms together with extrinsic factors, i.e. Treg cells, instigated during immunosuppression affect the magnitude and quality of the antiviral T cell responses and have important implications for protective vaccine development.