T. Kanto et al., Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals, J IMMUNOL, 162(9), 1999, pp. 5584-5591
In hepatitis C virus (HCV) infection, Th responses are implicated in the pa
thogenesis of liver disease, The dendritic cell (DC) is the most potent act
ivator of CD4 T cells for supporting Th1 differentiation. To clarify the ro
les of DC of HCV-infected individuals in the development of CD4 T cell resp
onses, we generated peripheral DC with GM-CSF and IL-4 from 24 chronic hepa
titis C patients and 14 healthy donors. We then compared their potentials f
or stimulating allogeneic CD4 T cells, autologous CDI T cells against influ
enza A or HCV core Ags, and cytokine production, The DC from the patients (
HCV-DC) expressed lower degrees of CD86 than DC from the donors (N-DC), whe
reas no difference was found in the HLA molecules and other costimulators.
HCV-DC stimulated allogeneic T cells less than N-DC; however, influenza A-
or core-pulsed HCV-DC retained the potentials for autologous T cell prolife
ration, In allogeneic DC/T cell cultures, the IFN-gamma levels with HCV-DC
were lower than those with N-DC, which may be related to the low expression
s of IL-12 p35 and p40 transcripts in HCV-DC. The stimulation with LPS disc
losed that HCV-DC is less patent in IL-12 p70 production than EI-DC. In the
autologous cultures, the pulsing of the,Ags to HCV-DC increased the IL-12
p40 and IFN-gamma production and up-regulated the transcription of both IL-
12 subunits, Exogenous IL-2 or IL-12 restored the low allogeneic T cell pro
liferation with HCV-DC in a dose-dependent manner. Therefore, low expressio
n of CD86 and/or IL-12 is crucially involved in the IOW allostimulatory cap
acity of HCV-DC, Low IL-12 and low IFN-gamma milieu with HCV-DC on encounte
rs with alloantigens may impede Th1 polarization.