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

 Young Joon Choi  ;  Sun Bean Kim  ;  Jong Hoon Kim  ;  Su-Hyung Park  ;  Moo Suk Park  ;  June Myung Kim  ;  Sang Hoon Han  ;  Eui-Cheol Shin 
 Experimental and Molecular Medicine, Vol.49(9) : e382, 2017 
Journal Title
 Experimental and Molecular Medicine 
Issue Date
Adult ; Aged ; Aged, 80 and over ; CD8-Positive T-Lymphocytes/immunology* ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/virology* ; Cytokines/metabolism ; Cytomegalovirus/physiology* ; Disease Susceptibility ; Female ; Humans ; Immunophenotyping ; Inflammation Mediators/metabolism ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Lymphocyte Count ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/metabolism ; Sepsis/diagnosis ; Sepsis/etiology* ; Severity of Illness Index ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Virus Activation/immunology* ; Young Adult
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-γ, TNF-α, and MIP-1β 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.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김종훈(Kim, Jong Hoon) ORCID logo https://orcid.org/0000-0002-3385-8180
김준명(Kim, June Myung)
박무석(Park, Moo Suk) ORCID logo https://orcid.org/0000-0003-0820-7615
한상훈(Han, Sang Hoon) ORCID logo https://orcid.org/0000-0002-4278-5198
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