Peripheral blood iNKT cell activation correlates with liver damage during acute hepatitis C
Tina Senff, Christopher Menne, Christine Cosmovici, Lia Laura Lewis-Ximenez, Jasneet Aneja, Ruth Broering, Arthur Y. Kim, Astrid M. Westendorf, Ulf Dittmer, Norbert Scherbaum, Georg M. Lauer, Jörg Timm
Tina Senff, Christopher Menne, Christine Cosmovici, Lia Laura Lewis-Ximenez, Jasneet Aneja, Ruth Broering, Arthur Y. Kim, Astrid M. Westendorf, Ulf Dittmer, Norbert Scherbaum, Georg M. Lauer, Jörg Timm
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Research Article Immunology Virology

Peripheral blood iNKT cell activation correlates with liver damage during acute hepatitis C

Abstract

Invariant NK T (iNKT) cells are implicated in viral clearance; however, their role in hepatitis C virus (HCV) infection remains controversial. Here, iNKT cells were studied during different stages of HCV infection. iNKT cells from patients with acute HCV infection and people who inject drugs (PWID) with chronic or spontaneously resolved HCV infection were characterized by flow cytometry. In a longitudinal analysis during acute HCV infection, frequencies of activated CD38+ iNKT cells reproducibly declined in spontaneously resolving patients, whereas they were persistently elevated in patients progressing to chronic infection. During the first year of infection, the frequency of activated CD38+ or CD69+ iNKT cells strongly correlated with alanine transaminase levels with particularly pronounced correlations in spontaneously resolving patients. Increased frequencies of activated iNKT cells in chronic HCV infection were confirmed in cross-sectional analyses of PWID with chronic or spontaneously resolved HCV infection; however, no apparent functional differences were observed with various stimulation protocols. Our data suggest that iNKT cells are activated during acute hepatitis C and that activation is sustained in chronic infection. The correlation between the frequency of activated iNKT cells and alanine transaminase may point toward a role of iNKT cells in liver damage.

Authors

Tina Senff, Christopher Menne, Christine Cosmovici, Lia Laura Lewis-Ximenez, Jasneet Aneja, Ruth Broering, Arthur Y. Kim, Astrid M. Westendorf, Ulf Dittmer, Norbert Scherbaum, Georg M. Lauer, Jörg Timm

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Figure 5

ILs enhance the expression of CD38 on iNKT cells, whereas type I IFNs induce an upregulation of CD1d on monocytes.

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ILs enhance the expression of CD38 on iNKT cells, whereas type I IFNs in...
(A) PBMCs from healthy donors were stimulated with IL-12, IL-15, and IL-18 for 24 hours, and the frequency of CD38+ iNKT cells was measured by flow cytometry (n = 10, paired t test). (B) Frequency of CD38+ iNKT cells after stimulation of PBMCs from healthy donors (n = 15) with IL-12, IL-15, and IL-18 or a combination of all 3 for 24 hours (1-way ANOVA, **P < 0.01). (C) CD1d mean fluorescence intensity (MFI) of various PBMC subsets was analyzed by flow cytometry. A representative experiment from 5 healthy donors is shown. (D and E) Healthy donor PBMCs were stimulated for 24 hours with 100 U/ml IFN-α2 or 1000 U/ml IFN-λ3 or were left untreated, followed by analysis of CD1d MFI of monocytes. Groups were compared by paired t test.