Lack of TGF-β production by hepatitis C virus-specific T cells during HCV acute phase is associated with HCV clearance in HIV coinfection.
OBJECTIVE
Immunity and genetic factors govern the recovery from acute hepatitis C virus (HCV) infection. No predictive factors have been yet identified in patients coinfected with the human immunodeficiency virus (HIV). We investigated whether early T cell responses to HCV producing transforming-growth-factor beta (TGF-β) predict the outcome of acute HCV coinfection, independently of the IL-28B gene polymorphism.


METHODS
Intracellular cytokine staining assays against HCV-core, E1, NS2, and NS4 overlapping peptides were used for the analysis of peripheral HCV-specific TGF-β-producing T cells. Patients were genotyped for IL-28B polymorphisms. Healthy donors' samples were tested as controls. Twenty-four acute hepatitis C-HIV+ patients were followed-up for 15 months defining two groups: (A) Recovered (n=16, 5 spontaneous recoveries, 11 sustained virologic response after treatment), (B) Chronic HCV (n=8, 4 spontaneous chronic course, 4 therapeutic failures).


RESULTS
During the acute pretreatment phase, core/NS2-specific TGF-β-producing CD4+ and/or CD8+ T cells were detected in 8/24 (33%) patients. Lack of anti-HCV TGF-β+ cells was characteristic of healthy donors and Group A, except for 2 cases, with frequencies significantly lower than in Group B (p=0.04 and 0.01), and was associated with recovery in 14/16 cases. Presence of anti-HCV TGF-β+ cells was associated with persistent viremia in 6/8 cases (p=0.005). This profile remained stable over time. Such TGF-β production was independent of the rs129679860 SNP (p=1.0) which was not associated with recovery (p=1.0).


CONCLUSIONS
During acute hepatitis C, pre-therapeutic HCV-specific TGF-β-producing T cells are a new marker independent of the IL-28B gene polymorphism, predicting the lack of spontaneous or therapeutic HCV clearance.
INSERM, UMRS-945, Laboratoire Immunité et Infection, Hôpital Pitié-Salpêtrière, F-75013 Paris, France.
Sawsan
S
Harfouch
Marguerite
M
Guiguet
Marc-Antoine
MA
Valantin
Assia
A
Samri
Zineb
Z
Ouazene
Laurence
L
Slama
Stéphanie
S
Dominguez
Anne
A
Simon
Ioannis
I
Theodorou
Vincent
V
Thibault
Brigitte
B
Autran
D000208:Acute Disease; D060085:Coinfection / Q000821:virology*; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007372:Interferons; D020381:Interleukin-17 / Q000096:biosynthesis; D007378:Interleukins / Q000235:genetics; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D000095022:Interferon Lambda
D007371:Interferon-gamma; D007372:Interferons; D020381:Interleukin-17; D007378:Interleukins; D016212:Transforming Growth Factor beta; C000624353:interferon-lambda, human; D000095022:Interferon Lambda