CD8+CD28-T-cells: Key cytotoxic players impacting disease pathogenesis in chronic HBV infection

During chronic hepatitis B (CHB), CD8+T-cells downregulate CD28, the primary costimulation molecule for T-cell activation. Diverse functional attributes of CD8+CD28-T-cells are suggested in various disease contexts. The present study aimed to characterize CD8+CD28-T-cells in different phases of chronic HBV infection (CHI)- Immune-tolerance (IT), hepatitis B e-antigen-positive CHB (EP-CHB), Inactive carriers (IC) and hepatitis B e-antigen-negative CHB (EN-CHB), to appraise their contribution in HBV-related disease pathophysiology. Flow cytometry analysis of T-cells in peripheral blood of study subjects revealed enhanced CD8+CD28-T-cell accumulation in EP-/EN-CHB, compared to IT/IC and they expanded equivalently in HBV-specific and non-specific CD8+T-cell compartments. Profound increase in CD8+CD28-T-cells expressing perforin/granzyme-B/CD57/IFN-/TNF-α and markers of terminal differentiation were observed exclusively in EP-/EN-CHB. Further, activation with anti-NKG2D resulted in heightened IFN-/TNF-α production selectively from CD8+CD28-T-cells, suggesting NKG2D-mediated alternative co-stimulation.  CD8+CD28-T-cells sorted from CHB patients induced enhanced apoptosis of PBMC, including CD4+T-cells. However, NKG2D-ligand (MICA/B) was preferentially expressed by HBV-specific CD4+T-cells of CHB patients, making these cells a potential target to NKG2D-dependant CD8+CD28-T-cell killing. Both CD28+ and CD28- T-cells in CHB expressed  CXCR3 at  si...

Source: Clinical Science - September 1, 2019 Category: Biomedical Science Authors: Nandi, M., Pal, S., Ghosh, S., Chakraborty, B. C., Dey, D., Baidya, A., Shil, A., Chattopadhyaya, S., Banerjee, S., Santra, A., Chowdhury, A., Datta, S. Tags: PublishAheadOfPrint Source Type: research