HCV persistence and immune evasion in the absence of memory T cell help

A Grakoui, NH Shoukry, DJ Woollard, JH Han… - Science, 2003 - science.org
A Grakoui, NH Shoukry, DJ Woollard, JH Han, HL Hanson, J Ghrayeb, KK Murthy, CM Rice…
Science, 2003science.org
Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-
term immunity to persistent viremia and associated liver diseases. Here, we report that
memory CD4+ Tcells are essential for this protection. Antibody-mediated depletion of CD4+
Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level
viremia despite functional intra-hepatic memory CD8+ Tcell responses. Incomplete control of
HCV replication by memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was …
Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4+ Tcells are essential for this protection. Antibody-mediated depletion of CD4+ Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8+ Tcell responses. Incomplete control of HCV replication by memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex–restricted epitopes and failure to resolve HCV infection.
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