CD8+ T cell depletion amplifies hepatitis C virus replication in peripheral blood mononuclear cells.
We investigated the ability of CD8+ T cells to inhibit hepatitis C virus (HCV) replication in peripheral blood mononuclear cells (PBMCs). PBMCs isolated from 11 of 20 HCV-infected subjects had no detectable HCV RNA. Removal of CD8+ T cells from these PBMCs resulted in detection of HCV RNA, and depletion of CD8+ T cells from PBMCs that had detectable HCV RNA amplified HCV replication. Reconstitution of CD8- PBMCs with autologous CD8+ T cells led to inhibition of HCV replication. Interferon-gamma produced by CD8+ T cells was partially responsible for CD8+ T cell-mediated noncytotoxic anti-HCV activity in PBMCs. This noncytotoxic anti-HCV activity was confirmed in HCV replicon cells. Supernatants from CD8+ T cell cultures inhibited HCV RNA expression in the replicon cells. These findings may have important implications for the immunopathogenesis of HCV in both immune and hepatic cells and are relevant to the development of host innate immunity-based anti-HCV interventions.
Li
Yuan
Y
Division of Allergy and Immunology, Department of Pediatrics, Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Wang
Xu
X
Douglas
Steven D
SD
Metzger
David S
DS
Woody
George
G
Zhang
Ting
T
Song
Li
L
Ho
Wen-Zhe
WZ
D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008212:Lymphocyte Depletion; D012367:RNA, Viral / Q000032:analysis; D014779:Virus Replication
D000998:Antiviral Agents; D012367:RNA, Viral; D007371:Interferon-gamma