Features and distribution of CD8 T cells with human leukocyte antigen class I-specific receptor expression in chronic hepatitis C.
CD8(+) T cells represent a sizable component of the liver inflammatory infiltrate in chronic hepatitis C and are thought to contribute to immune-mediated tissue injury. Because chronic stimulation may promote the expression by CD8(+) T cells of distinct human leukocyte antigen class I-specific natural killer cell receptors (NKRs) susceptible to both inhibiting effector functions and promoting cell survival, we examined the distribution and characteristics of CD8(+) T cells with such receptors in chronic hepatitis C patients. NKR CD8(+) T cells were detectable in liver and peripheral blood from hepatitis C virus (HCV)-infected patients but were not major subsets. However, the frequency of NKG2A(+) CD8(+) in the liver and in a lesser extent in the peripheral blood was positively correlated to histological activity in HCV-infected patients. No such correlation was found with KIR(+) T cells in liver in HCV-infected patients and with the both NKR CD8(+) T cells in hepatitis B virus (HBV) infected patients. Circulating CD8(+) T cells expressing KIRs exhibited phenotypic features of memory T cells with exacerbated expression of the senescence marker CD57 in patients. NKG2A(+)CD8(+) T cells were committed T cells that appeared less differentiated than KIR(+)CD8(+) T cells. In HCV-infected patients, their content in perforin was low and similar to that observed in NKG2A(-)CD8(+) T cells; this scenario was not observed in healthy subjects and HBV-infected patients. Both NKG2A and KIRs could inhibit the response of HCV-specific CD8(+) T cells ex vivo.


CONCLUSIONS
These results support the concept that an accumulation in the liver parenchyma of NKR(+)CD8(+) T cells that have functional alterations could be responsible for liver lesions. They provide novel insights into the complexity of liver-infiltrating CD8(+) T cells in chronic hepatitis C and reveal that distinct subsets of antigen-experienced CD8(+) T cells are differentially sensitive to the pervasive influence of HCV.
Institut National de la Santé et de la Recherche Médicale Unité 548, Département Réponse et Dynamique Cellulaires, Commissariat à l'Energie Atomique, Université Joseph Fourier, Grenoble, France.
Paula
P
Bonorino
Vincent
V
Leroy
Tania
T
Dufeu-Duchesne
Stefania
S
Tongiani-Dashan
Nathalie
N
Sturm
Martine
M
Pernollet
Eric
E
Vivier
Jean-Pierre
JP
Zarski
Patrice N
PN
Marche
Evelyne
E
Jouvin-Marche
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054353:Perforin / Q000378:metabolism; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism*; D054342:Receptors, KIR2DL1 / Q000378:metabolism*; D054344:Receptors, KIR2DL3 / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell
D015395:Histocompatibility Antigens Class I; C527054:KLRC1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell; D054353:Perforin