Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms.
Hallmark of acute hepatitis C virus (HCV) infection is a severe virus-specific effector CD8(+) T cell dysfunction that seems to be a critical factor in preventing the resolution of infection and in favoring the onset of chronic liver immunopathology. We suggest that this dysfunction is critical in the establishment of HCV persistence, unless it is compensated by multispecific responses, as found in individuals resolving infection. Analyses on purified populations indicate that central memory HCV-specific CCR7(+)/CD8(+) T cells efficiently proliferate and differentiate in vitro, although the large population of memory effector CCR7(-) cells found in the peripheral blood of acutely infected patients display poor effector functions ex vivo (semi-effectors). However, we report strong evidence in support of IL-2 being capable of pushing semi-effector CTL to complete their effector cell program. Therefore, IL-2 deficiency during T cell activation may be responsible for the dichotomy between memory CTL expansion and incomplete effector differentiation shown in patients with acute HCV infection. These data are consistent with the possible therapeutic treatment with IL-2 to rebuild the effector T cell pool in these patients.
Francavilla
Vittorio
V
Fondazione Andrea Cesalpino and Dipartimento di Medicina Interna, Università degli Studi di Roma La Sapienza, Rome, Italy.
Accapezzato
Daniele
D
De Salvo
Marietta
M
Rawson
Pisana
P
Cosimi
Olivia
O
Lipp
Martin
M
Cerino
Antonella
A
Cividini
Agostino
A
Mondelli
Mario U
MU
Barnaba
Vincenzo
V
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology* / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D000998:Antiviral Agents; C515370:CCR7 protein, human; D007376:Interleukin-2; D054400:Receptors, CCR7; D019707:Receptors, Chemokine