Functional reconstitution of defective myeloid dendritic cells in chronic hepatitis C infection on successful antiviral treatment.
OBJECTIVE
Poor cellular trafficking and suboptimal T-cell responses in liver, the hall marks of chronic hepatitis C virus (CHC) infection, might be attributed to defective antigen presentation. Controversy exists regarding role of myeloid dendritic cells (DCs) in CHC and response to antiviral treatment. This study examines functional status of DCs before and after completion of treatment with the aim to find any modulatory effect.


METHODS
Frequency and functions of monocyte-derived DCs (mo-DCs) were evaluated in CHC (n = 25), before the start of therapy (CHC(0) ). These patients were then put on treatment with peg-interferon-α plus ribavirin for 24 or 48 weeks, and the mo-DC functions were evaluated after 6 months of completion of treatment (CHC(6) ) again, using multicolour flow cytometry, endocytosis assay, cytokine assay and mixed lymphocyte reaction.


RESULTS
Pre-treatment frequency of mo-DCs in CHC(0) was lower than that in healthy controls, which became close to normal in patients who achieved virological response (SVR+, n = 20) but not in non-responders (SVR-, n = 5). Pre-treatment levels of CD83, CD80 and CD86 on mo-DC in SVR(0) +, but not SVR(0) -, got upregulated after lipopolysaccharide stimulation supporting the hypothesis that DCs play deciding role in response to therapy. Post-treatment allostimulatory and phagocytosing capacity of mo-DCs in SVR+ patients indicated regain in functional capacity in these patients but not in SVR- patients.


CONCLUSIONS
Our results indicate that DCs in CHC patients exhibiting mature and functional phenotype prior to therapy achieve sustained virological response suggesting that functional modulation of defective DCs is directly associated with successful response to therapy.
Department of Immunopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Deepa
D
Rana
Yogesh K
YK
Chawla
Ajay
A
Duseja
Radhakrishan
R
Dhiman
Sunil K
SK
Arora
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D000998:Antiviral Agents / Q000627:therapeutic use*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult; D000097802:CD83 Antigen
D015703:Antigens, CD; D000998:Antiviral Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007136:Immunoglobulins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D000097802:CD83 Antigen; C497964:CD86 protein, human; C100416:peginterferon alfa-2a