Immunology

Biography

Biography: Iulia Popescu

Abstract

CMV remains an important opportunistic pathogen in solid organ transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor+/recipient-; D+R-) are at high-risk for active CMV infection and increased mortality; however the immune correlates of viral control remain incompletely understood. We prospectively studied 23 D+R- LTRs during primary CMV infection to determine whether acute CD8+ T-cell parameters differentiated the capacity for viral control in early chronic infection. T-box transcription factors expression patterns of T-bet >Eomes differentiated LTR controllers from viremicrelapsers, and reciprocally correlated with granzyme B loading, and CMV phosphoprotein 65 (pp65)-specific CD8+IFN-+ and CD107a+ frequencies. LTR relapsers demonstrated reduced CD8+Ki67+ cells ex vivo and substantially impaired CD8+pp65-specific in vitro proliferative responses at 6 days, with concomitantly lower pp65-specific CD4+IL-2+ frequencies, as compared to LTR controllers. However, CMV-specific in vitro proliferative responses could be significantly rescued, most effectively with pp65 antigen and exogenous IL-2, resulting in an increased T-bet:Eomes balance, and enhanced effector function. Using class I CMV tetramers, we observed similar frequencies between relapsers and controllers, though reduced T-bet: Eomes balance in tetramer+ cells from relapsers, along with impaired CD8+ effector responses to tetramer-peptide re-stimulation. Together, these data show impaired CMV-specific CD8+ effector responses is not for complete lack of CMV-specific cells, but rather, underscores the importance of the T-bet:Eomes balance, with CMV-specific proliferation a key factor driving early T-bet expression and effector function in CD8+ T cells during primary infection, and differentiating the capacity of high-risk LTRs to establish immune control during early chronic infection.