Impaired polyfunctionality of CD8(+) T cells in severe sepsis patients with human cytomegalovirus reactivation

Abstract

Human cytomegalovirus (HCMV) establishes a lifelong chronic latent infection and often reactivates in immunocompromised patients. In addition, HCMV reactivates in patients with sepsis or other critical illnesses, particularly in patients with poor prognoses. However, the immunological characteristics of sepsis patients with HCMV reactivation have not been elucidated. In the present study, we examined T-cell responses in severe sepsis patients with and without HCMV reactivation. First, HCMV pp65-specific T-cell functions were assessed by intracellular cytokine staining (ICS) for IFN-gamma, TNF-alpha, and MIP-1 beta and by CD107a staining. We analyzed the ICS data for each function individually and found no difference between the patient groups. However, the relative frequency of polyfunctional CD8(+) T cells was significantly decreased in sepsis patients with HCMV reactivation. Next, we examined programmed cell death protein 1 (PD-1) expression. It was significantly increased in the CD8(+) T-cell population in severe sepsis patients with HCMV reactivation, indicating CD8(+) T-cell exhaustion. Interestingly, the frequency of PD-1(+) cells in the CD8(+) T-cell population was inversely correlated with the relative frequency of polyfunctional CD8(+) T cells. Herein, we demonstrate that HCMV reactivation in severe sepsis patients is associated with PD-1 expression and impaired polyfunctionality of CD8(+) T cells.