title: A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression.
abstract: OBJECTIVE
  The lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68+ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68+ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression.
  
  
  METHODS
  CD80, CD86 and PD-L1 expression by CD68+ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry.
  
  
  RESULTS
  The count of CD68+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68+CD80+ cells and CD68+PD-L1+ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68+CD80+ cells was higher than that of CD68+CD86+ and CD68+PD-L1+ cells. In addition, the frequencies of CD68+CD80+ and CD68+CD86+ cells were higher in the lobular areas than the portal areas.
  
  
  CONCLUSIONS
  Our results show that CD68+ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Elias A
authors.initials: EA
authors.lastname: Said
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Iman
authors.initials: I
authors.lastname: Al-Reesi
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Marwa
authors.initials: M
authors.lastname: Al-Riyami
authors.affiliation: Department of Medicine, Armed Forces Hospital, Muscat, Oman.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Naamani
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Shadia
authors.initials: S
authors.lastname: Al-Sinawi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Al-Balushi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Koh
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Juma Z
authors.initials: JZ
authors.lastname: Al-Busaidi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Idris
authors.affiliation: Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Al-Jabri
mesh_terms: D000328:Adult; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000378:metabolism*; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human