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+/recipient2; D+R2) 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.