title: Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B.
abstract: OBJECTIVE
  Lamivudine therapy in patients with chronic hepatitis B can induce the recovery of antiviral T cell responses. It is unknown whether the recovery of T cell responsiveness is long-lasting and persists throughout the treatment and whether the elevation of viremia which follows therapy withdrawal can restore a condition of T cell unresponsiveness.
  
  
  METHODS
  Frequency and function of circulating hepatitis B virus (HBV)-specific CD4 and CD8 cells from 12 hepatitis e surface antigen + patients with chronic hepatitis B were studied longitudinally before, during and after lamivudine therapy by intracellular cytokine staining, proliferation and cytotoxicity assays against HBV proteins and peptides. CD4-mediated responses were analyzed in all patients, whereas CD8 cells were studied in 6 HLA-A2+ patients.
  
  
  RESULTS
  HBV-specific CD4 and CD8 reactivity showed a bi-phasic behavior under lamivudine therapy with an early enhancement of T cell frequency and intensity of responses followed by a persistent decline starting from the 5th to 6th month of treatment.
  
  
  CONCLUSIONS
  Since restoration of HBV-specific T cell reactivity is only transient, our study indicates that therapeutic stimulation of HBV-specific T cell responses to complement lamivudine treatment should be done early after the initiation of lamivudine. Moreover, the transient nature of the immune reconstitution may represent a favorable condition for virus reactivation once lamivudine therapy is withdrawn.
authors.affiliation: Divisione Malattie Infettive ed Epatologia, Azienda Ospedaliera di Parma, Via Gramsci 14, 43100 Parma, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Boni
authors.forename: Amalia
authors.initials: A
authors.lastname: Penna
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lamonaca
authors.forename: Irene
authors.initials: I
authors.lastname: Rapti
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.forename: Massimo
authors.initials: M
authors.lastname: Pilli
authors.forename: Simona
authors.initials: S
authors.lastname: Urbani
authors.forename: Albertina
authors.initials: A
authors.lastname: Cavalli
authors.forename: Simona
authors.initials: S
authors.lastname: Cerioni
authors.forename: Ruggero
authors.initials: R
authors.lastname: Panebianco
authors.forename: Julian
authors.initials: J
authors.lastname: Jenkins
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D013745:Tetanus Toxoid / Q000494:pharmacology; D013997:Time Factors
chemical_list: D008934:Mitogens; D010835:Phytohemagglutinins; D018894:Reverse Transcriptase Inhibitors; D013745:Tetanus Toxoid; D019259:Lamivudine