Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus‐specific CD4⁺ T‐cell proliferation in patients with hepatitis C virus infection

Abstract

+ T-cell proliferation was less frequent and vigorous in CHC than in HSP patients and was directly related to the number of PBDCs and their IL-12 production but inversely related to their IL-10 production. Taken together, these results seem to suggest that cytokines of DC origin contribute to the regulation of HCV-specific immunity in CHC patients and indicate that PBDCs may represent a novel non-invasive tool for immune monitoring of these patients.

Dendritic cells in chronic viral hepatitis B and C: victims or guardian angels?

“…Also the levels of TNFα in response to double-stranded RNA and LPS were found to be reduced, whereas the production of IL-6 was normal 31 64. The production of the immune regulatory cytokine IL-10 was enhanced in mDCs from patients with chronic HCV infection as compared with healthy individuals 65 66. This altered cytokine profile could explain the decreased capacity to induce allogeneic T cell proliferation,65 67 68 but others were unable to reproduce these findings 69 70.…”

Dendritic cells, regulatory T cells and the pathogenesis of chronic hepatitis C

“…Regardless of their distribution (i.e., liver vs. peripheral blood), contradictory data indicate that functions of pDCs and mDCs are either intact 56 - 63 or impaired 36 , 39 , 42 , 44 , 48 , 64 - 74 in patients with chronic hepatitis C. Functional impairments include: decreased IFN-α and IL-12 secretion, increased IL-10 production, lowered expression of HLA-DR and costimulatory molecules such as CD86, decreased allostimulatory activity and increased ability to prime T reg cells 36 , 39 , 42 , 44 , 48 - 50 , 64 , 65 , 67 - 69 , 75 - 79 . Additional studies reported that DCs obtained from chronically-infected patients were phenotypically immature and failed to upregulate maturation (costimulatory) markers in response to stimuli such as TNF-α 66 , 73 .…”

“…Circulating pDCs in chronic HCV-infected patients exhibit: diminished HLA-DR expression, a markedly reduced capacity to secrete IFN-α and, consequently, decreased anti-viral potency 36 , 39 , 44 , 67 , 68 , 80 . mDCs in chronic HCV infections secrete significantly lower levels of IL-12 and increased concentrations of IL-10, which tends to skew the immune response toward tolerance and a reduced ability to induce T-cell proliferation and T h1 polarization 36 , 47 , 49 , 67 , 69 , 72 , 75 - 77 , 81 . The stimulatory potential of mDCs and the alloreactive response of CD4 + T cells are also diminished in chronic HCV infections 44 .…”

Case‐crossover study of hospitalization for acute hepatitis in Chinese herb users

“…Part of idiosyncratic reaction is related to hypersensitivity or immunological response 29 . This immune mechanism of liver injury might be different in patients with HBV or HCV infection 30,31 . However, the hepatotoxic mechanisms and possible interactions with chronic HBV and HCV infection require further study.…”