Modulación de la expresión de los receptores de quimioquinas CCR5 y CXCR3 en las células T CD8+ durante el tratamiento de la infección crónica por virus de la hepatitis C y su correlación con el desarrollo de respuesta virológica sostenida

  1. Miquel Plaza, Joaquin
unter der Leitung von:
  1. Juan Ramón Larrubia Marfil Doktorvater/Doktormutter

Universität der Verteidigung: Universidad de Alcalá

Fecha de defensa: 13 von Oktober von 2010

Gericht:
  1. Agustín Albillos Martínez Präsident/in
  2. Jesús Javier Mateos Hernández-Briz Sekretär/in
  3. José María Ladero Quesada Vocal
  4. Silvia García Garzón Vocal
  5. Conrado M. Fernández Rodriguez Vocal

Art: Dissertation

Zusammenfassung

AIMS: CXCR3 and CCR5 play a major role in recruiting cytotoxic T cells (Tc) and secreting secondary type 1 cytokines (Tc1) in the liver. HCV could impair their expression as a survival mechanism. The role of these chemokine receptors on CD8+ cells in chronic hepatitis C is analysed. METHODS: Serum, chemokines, peripheral blood and intrahepatic lymphocytes from chronic hepatitis C patients were studied. CXCR3 / CCR5 expressing CD8+ cells were quantified by flow-cytometry. Serum chemokines concentration (CXCL10/CCL3) was measured by ELISA. Basal data were correlated with liver inflammation. Longitudinal data were obtained during treatment and correlated with virologic response. RESULTS: CCR5/CXCR3 expressing CD8+ cells were enriched in the liver and correlated with inflammation. Chronic HCV patients presented the same frequency of CCR5high/CXCR3high expressing CD8+ cells in peripheral blood as in healthy controls but higher serum concentration of CXCL10/CCL3. Treatment with PEGinterferon a-2b plus ribavirin increased CCR5high/CXCR3high expressing CD8+ cells frequency in peripheral blood and decreased CXCL10/CCL3 serum concentration. Increase in CXCR3high expressing CD8+ cells after 24 weeks of treatment was correlated with SVR. CONCLUSIONS: In chronic hepatitis C, anti-viral treatment induces an increase in CD8+ cells expressing chemokine receptors associated with Tc1 response and a reduction in their ligands. Achievement of viral control is associated with an increase in CXCR3high expressing CD8+ cells during treatment.