Human Immunodeficiency Virus-Human Pegivirus Coinfected Individuals Display Functional Mucosal-Associated Invariant T Cells and Follicular T Cells Irrespective of PD-1 Expression.

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.