Altered T cell costimulation during chronic hepatitis B infection.
T-cell response to hepatitis B virus (HBV) is vigorous, polyclonal and multi-specific in patients with acute hepatitis who ultimately clear the virus, whereas it is narrow and inefficient in patients with chronic disease, where inappropriate early activation events could account for viral persistence. We investigated the induction of activation receptors and cytokine production in response to HBcAg and crosslinking of CD28 molecules, in CD4+ cells from a group of chronically infected patients (CIP) and naturally immune subjects (NIS). We demonstrated that CD4+ cells from CIP did not increase levels of CD40L and CD69 following stimulation with HBcAg alone or associated to CD28 crosslinking, in contrast to subjects that resolved the infection (p<0.01). Furthermore, CD4+ cells from CIP produced elevated levels of IL-10 in response to HBcAg. These results suggest that a predominant inhibitory environment may be responsible for altered T cell costimulation, representing a pathogenic mechanism for viral persistence.
Institute of Clinical Immunology, University of Los Andes, Mérida-Venezuela.
Luisa
L
Barboza
Siham
S
Salmen
Darrell L
DL
Peterson
Henry
H
Montes
Melisa
M
Colmenares
Manuel
M
Hernández
Leidith E
LE
Berrueta-Carrillo
Lisbeth
L
Berrueta
D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008875:Middle Aged; D013745:Tetanus Toxoid / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D023201:CD40 Ligand; D016207:Cytokines; D006512:Hepatitis B Core Antigens; D016753:Interleukin-10; D015759:Ionomycin; D007476:Ionophores; D037181:Lectins, C-Type; D013745:Tetanus Toxoid; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens; C016658:phorbolol myristate acetate