Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Dynamics of CD8+ T cell responses in HCV infection

Our strategies is that: 1) to restore mechanisms subverting CTL responses in chronic infections and 2) to enhance cross-presentation of soluble antigens.

Concerning the point 1, we found direct evidence that both HCV and host determinants play a critical role in establishing a status of chronic low-level liver inflammation. Indeed, we found that circulating HCV core protein (HCVcore) inhibited the signal transduction pathway instrumental for IL-2 production, in turn essential for the full effector cell differentiation, and provided direct evidence of the existence of virus-specific CCR7-CD8+ regulatory T cells.

These cells infiltrate the liver in chronically HCV-infected patients, and control hepatic effector CD8+ T cell responses via the production of IL-10. Thus HCV-core antagonists or IL-10 inihibitors may represent important targets for restoring the antiviral responses in HCV infection.

As regards the mechanisms of cross-priming CD8+ T cell responses by DC (point 2), we set up a valid cross-presentation assay of soluble antigens by DCs and demonstrated that efficient cross-presentation of soluble antigens requires that the latter are protected from the endosomal processing machinery. This evidence suggests it could be exploited for the design of innovative strategies eliciting protective CD8 immunity.

Informazioni correlate

Reported by

Fondazione Andrea Cesalpino - University of Rome "La Sapienza"
Policlinico "Umberto I", viale del Policlinico 155
00199 Rome
See on map