Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68.sup.+ Cells during Chronic HBV Infection

• Published in: PloS one 2016-06, Vol.11 (6)
• 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: Complications and side effects; Gene expression; Hepatitis B virus; Liver cirrhosis; Risk factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158265

The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68.sup.+ cells has not been explored in HBV-infected livers. Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. Chronic HBV infection was associated with increased CD68.sup.+ CD86.sup.+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68.sup.+ CD80.sup.+ and CD68.sup.+ PD-L1.sup.+ cells, compared to the control group. While CD68.sup.+ CD80.sup.+ cell count in portal areas correlated with the fibrosis score, CD68.sup.+ CD80.sup.+ cell percentage in lobular areas correlated with the inflammation grade. The upregulation of CD86 but not CD80 and PD-L1 on CD68.sup.+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68.sup.+ cells correlates with liver inflammation and fibrosis.