Hepatic expansion of a virus-specific regulatory CD8(+) T cell population in chronic hepatitis C virus infection.
Regulatory T (T(R)) cells consist of phenotypically and functionally distinct CD4(+) and CD8(+) T cell subsets engaged both in maintaining self-tolerance and in preventing anti-non-self effector responses (microbial, tumor, transplant, and so on) that may be harmful to the host. Here we propose that the proinflammatory function of virus-specific memory effector CCR7(-)CD8(+) T cells, which are massively recruited in the liver, are inefficient (in terms of IFN-gamma production) in patients with chronic hepatitis C virus (HCV) infection because of the concomitant presence of virus-specific CCR7(-)CD8(+) T(R) cells producing considerable amounts of IL-10. These CD8(+) T(R) cells are antigen specific, as they can be stimulated by HCV epitopes and suppress T cell responses that are in turn restored by the addition of neutralizing anti-IL-10. This study provides for the first time to our knowledge direct evidence of the existence of virus-specific CD8(+) T(R) cells that infiltrate the livers of patients with chronic HCV infection, identifies IL-10 as a soluble inhibitory factor mediating suppression, and suggests that these cells play a pivotal role in controlling hepatic effector CD8(+) T cell responses.
Accapezzato
Daniele
D
Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna, Università degli Studi di Roma La Sapienza, Rome, Italy.
Francavilla
Vittorio
V
Paroli
Marino
M
Casciaro
Marco
M
Chircu
Lucia Valeria
LV
Cividini
Agostino
A
Abrignani
Sergio
S
Mondelli
Mario U
MU
Barnaba
Vincenzo
V
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008875:Middle Aged; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016753:Interleukin-10