Abstract
Human pegivirus (HPgV) appears to alter the prognosis of HIV disease by modulating T cell homeostasis, chemokine/cytokine production, and T cell activation. In this study, we evaluated if HPgV had any 'favorable' impact on the quantity and quality of T cells in HIV-infected individuals. T cell subsets such as CD4(lo), CD4(hi), and CD8(+) T cells, CD4(+) MAIT cells, CD8(+) MAIT cells, follicular helper T (TFH) cells, and follicular cytotoxic T (TFC) cells were characterized based on the expression of markers associated with immune activation (CD69, ICOS), proliferation (ki67), cytokine production (TNF-α, IFN-γ), and exhaustion (PD-1). HIV(+)HPgV(+) individuals had lower transaminase SGOT (liver) and GGT (biliary) in the plasma than those who were HPgV(-). HIV/HPgV coinfection was significantly associated with increased absolute CD4(+) T cell counts. HIV(+)HPgV(+) and HIV(+)HPgV(-) individuals had highly activated T cell subsets with high expression of CD69 and ICOS on bulk CD4(+) and CD8(+) T cells, CD4(+) MAIT cells, CD8(+) MAIT cells, and CXCR5(+)CD4(+) T cells and CXCR5(+)CD8(+) T cells compared with healthy controls. Irrespective of immune activation markers, these cells also displayed higher levels of PD-1 on CD4(+) T and CD8(+) T cells . Exploring effector functionality based on mitogen stimulation demonstrated increased cytokine production by CD4(+) MAIT and CD8(+) MAIT cells. Decrease in absolute CD4(+) T cell counts correlated positively with intracellular IFN-γ levels by CD4(lo) T cells, whereas increase of the same correlated negatively with TNF-α in the CD4(lo) T cells of HIV(+)HPgV(+) individuals. HIV/HPgV coinfected individuals display functional CD4(+) and CD8(+) MAIT, TFH, and TFC cells irrespective of PD-1 expression.