ICOS-expressing Treg are required for resolution of CD8-mediated lung injury (P2198)

Abstract

Abstract Long-term survival of lung allograft recipients can be hindered by the development of obliterative bronchiolitis (OB), a condition that has been linked to acute rejection. CD8+ T cells contribute to acute rejection by inducing lung epithelial injury; however, the mechanisms for mitigating this type of injury are unclear. Using an in vivo model of CD8-mediated lung rejection, we have found bystander CD4+ T cells are required for resolution of acute inflammation. The percentage of CD4+Foxp3+ Treg is significantly higher in inflamed lungs compared to controls, and the majority of these cells are ICOSHi in inflamed lungs. To determine the role ICOS expression plays in the ability of Treg to control inflammation, we investigated Treg cytokine expression levels and found WT Treg express more Il10 than Icos-/- Treg when stimulated in vitro. IL-10 production is also enhanced in WT Treg compared to Icos-/- Treg. Additionally, we saw WT Treg have enhanced proliferation compared to Icos-/- Treg. In vivo, we found Icos-/- CD4+ T cells are not sufficient for resolution of acute inflammation; however, addition of WT Treg rescues this defect. Together, these data suggest ICOS-expressing Treg are required for resolution of CD8-mediated lung injury due to a possible increase in IL-10 production or an enhanced ability to proliferate in vivo. Augmenting ICOS function on Treg after transplantation may protect the lung from acute rejection and prevent OB.