Early KLRG1+ but Not CD57+CD8+ T Cells in Primary Cytomegalovirus Infection Predict Effector Function and Viral Control

CMV remains an important opportunistic pathogen in high-risk lung transplant recipients. We characterized the phenotype and function of CD8 + T cells from acute/primary into chronic CMV infection in 23 (donor+/recipient-; D+R-) lung transplant recipients and found rapid induction of both KLRG1 + and/or CD57 + CMV-specific CD8 + T cells with unexpected coexpression of CD27. These cells demonstrated maturation from an acute effector T cell (T AEFF ) to an effector memory T cell (T EM ) phenotype with progressive enrichment of KLRG1 + CD57 + CD27 - cells into memory. CMV-specific KLRG1 + T AEFF were capable of in vitro proliferation that diminished upon acquisition of CD57, whereas only KLRG1 + expression correlated with T-bet expression and effector function. In contrast to blood T AEFF , lung mucosal T AEFF demonstrated reduced KLRG1/T-bet expression but similar CD57 levels. Additionally, increased KLRG1 + T AEFF were associated with early immune viral control following primary infection. To our knowledge, our findings provide new insights into the roles of KLRG1 and CD57 expression in human T cells, forming the basis for a refined model of CD8 + T cell differentiation during CMV infection.