Enhanced ability of peripheral invariant natural killer T cells to produce IL-13 in chronic hepatitis C virus infection.
OBJECTIVE
Human invariant natural killer T (iNKT) cells express a TCR Valpha24-JalphaQ paired with Vbeta11 and are activated by a surrogate ligand, alpha-galactosylceramide (alphaGalCer). The iNKT cells are involved in the regulation of anti-viral immune responses; however, little is known about their roles in hepatitis C virus (HCV) infection.


METHODS
We compared the frequency of peripheral iNKT cells and their cytokine producing capacity reactive to alphaGalCer between chronically HCV-infected patients and healthy subjects. Cytokine production of freshly isolated iNKT cells were analyzed by ELISPOT. Activated iNKT cells were obtained by culture with alphaGalCer-loaded dendritic cells (DCs) and re-stimulated with them for the measurement of cytokine production.


RESULTS
The frequencies of iNKT cells were not different between HCV-infected patients and healthy subjects. The number of fresh IFN-gamma-producing iNKT cells reactive to alphaGalCer was not different between the patients and controls, whereas fresh iNKT cells produced negligible amounts of Th2 cytokines regardless of HCV infection. In response to alphaGalCer, expanded iNKT cells from the patients secreted IFN-gamma comparable in amount to controls, whereas they released significantly more IL-13 than cells from controls.


CONCLUSIONS
Activated iNKT cells from HCV-infected patients gain more ability to secrete IL-13 than those from healthy subjects.
Department of Dendritic Cell Biology and Clinical Application, Osaka University Graduate School of Medicine, Osaka, Japan.
Michiyo
M
Inoue
Tatsuya
T
Kanto
Hideki
H
Miyatake
Ichiyo
I
Itose
Masanori
M
Miyazaki
Takayuki
T
Yakushijin
Mitsuru
M
Sakakibara
Noriyoshi
N
Kuzushita
Naoki
N
Hiramatsu
Tetsuo
T
Takehara
Akinori
A
Kasahara
Norio
N
Hayashi
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
D015415:Biomarkers; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma