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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3171-3176
IMMUNOBIOLOGY
Impaired dendritic cell maturation in patients with chronic, but
not resolved, hepatitis C virus infection
Susanne Auffermann-Gretzinger,
Emmet B. Keeffe, and
Shoshana Levy
From the Divisions of Oncology and of Gastroenterology
and Hepatology, Department of Medicine, Stanford University Medical
Center, Stanford, CA.
Dendritic cells (DCs) are important for the initiation of immune
responses to foreign antigens. Their antigen uptake and presentation capacities enable them to prime and activate T cells. Immature DCs
capture antigens; however, they must be activated to mature before
serving as efficient antigen-presenting cells. The antigen-presenting capacity of DCs can be diminished during viral infection and as a
consequence of tumor formation. Chronic infection with hepatitis C
virus (HCV) has been shown to affect the allostimulatory function of
DCs. In this study, it is demonstrated that monocyte-derived DCs from
patients with chronic HCV infection do not respond to maturation
stimuli. Instead, they maintain their immature phenotype, reflected by
the pattern of cell surface markers and by their continued capacity to
uptake antigen. Moreover, their allostimulatory abilities are impaired
compared with those of mature DCs derived from healthy donors. To
investigate a possible correlation between viral clearance and this DC
maturation defect, patients with resolved HCV infection after a course
of antiviral therapy were studied. Results demonstrate that DCs from
patients who cleared HCV behaved like DCs from healthy donors: in
response to maturation stimuli, they decrease antigen uptake,
up-regulate expression of appropriate surface markers, and are potent
stimulators of allogeneic T cells.

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