A Potential Inhibitory Profile of Liver CD68.sup.+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression

• Published in: PloS one 2016-04, Vol.11 (4)
• Main Authors: Said, Elias A, Al-Reesi, Iman, Al-Riyami, Marwa, Al-Naamani, Khalid, Al-Sinawi, Shadia, Al-Balushi, Mohammed S, Koh, Crystal Y, Al-Busaidi, Juma Z, Idris, Mohamed A, Al-Jabri, Ali A
• Format: Article
• Language: English
• Subjects: Fibrosis; Health aspects; Hepatitis C virus; Hepatocellular carcinoma; Immune system; Macrophages; Risk factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153191

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.sup.+ 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.sup.+ 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.sup.+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression. CD80, CD86 and PD-L1 expression by CD68.sup.+ 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. The count of CD68.sup.+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68.sup.+ CD80.sup.+ cells and CD68.sup.+ PD-L1.sup.+ 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.sup.+ CD80.sup.+ cells was higher than that of CD68.sup.+ CD86.sup.+ and CD68.sup.+ PD-L1.sup.+ cells. In addition, the frequencies of CD68.sup.+ CD80.sup.+ and CD68.sup.+ CD86.sup.+ cells were higher in the lobular areas than the portal areas. Our results show that CD68.sup.+ 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.