Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus-specific CD4+ T-cell proliferation in patients with hepatitis C virus infection |
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| Authors: | Della Bella Silvia Crosignani Andrea Riva Antonio Presicce Pietro Benetti Alberto Longhi Renato Podda Mauro Villa Maria L |
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| Affiliation: | 1Dipartimento di Scienze e Tecnologie Biomediche, Cattedra di Immunologia, Università degli Studi di Milano, Milan, Italy;2Department of Medicine, Surgery and Dentistry, School of Medicine San Paolo; University of Milan, Milan, Italy;3Istituto di Chimica del Riconoscimento Molecolare, CNR, Milan, Italy |
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| Abstract: | ![]()
Through the production of stimulatory and suppressive cytokines, dendritic cells (DCs) regulate virus-specific immune responses that are crucial to virus eradication. To explore a possible role of DCs in the persistence of hepatitis C virus (HCV) infection, in this study we analysed peripheral blood DCs (PBDCs) in patients with chronic hepatitis C (CHC) compared with those in both healthy seronegative (HSN) controls and a group of subjects who had spontaneously resolved infection, defined as healthy HCV-seropositive (HSP), and we evaluated the relationships between PBDCs and HCV-specific CD4(+) T-cell reactivity. The number of PBDCs, their immunophenotype and expression of regulatory cytokines were evaluated by flow cytometry on whole-blood samples. HCV-specific CD4(+) T-cell activation, proliferation and cytokine production were evaluated in cultures of peripheral blood mononuclear cells (PBMCs) stimulated in vitro with HCV peptides. We found that PBDCs from CHC subjects were numerically reduced and showed lower interleukin-12 (IL-12) and higher IL-10 expression than those from HSN controls. PBDCs from HSP subjects were similar to those from HSN controls. HCV-specific CD4(+) 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. |
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| Keywords: | hepatitis C virus peripheral blood dendritic cells interleukin-10 interleukin-12 T-cell proliferation |
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