Association of interleukin-15-induced peripheral immune activation with hepatic stellate cell activation in persons coinfected with hepatitis C virus and HIV.
Hepatic stellate cells (HSCs) mediate hepatitis C virus (HCV)-related liver fibrosis, and increased HSC activation in human immunodeficiency virus (HIV)/HCV coinfection may be associated with accelerated fibrosis. We examined the level of HSC activation in HIV/HCV-coinfected and HCV-monoinfected subjects and its relationship to the level of activation and gene expression of peripheral immune cells in coinfected subjects. HSC activation levels positively correlated with peripheral CD4+ and CD8+ T cell immune activation and were associated with enhanced interleukin-15 (IL-15) gene expression, suggesting a pathogenic role for IL-15-driven immunomediated hepatic fibrosis. Future strategies that reduce immune activation and HSC activation may delay progression of liver fibrosis.
Allison
Robert D
RD
Department of Transfusion Medicine, National Institutes of Health, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-1876, USA.
Katsounas
Antonios
A
Koziol
Deloris E
DE
Kleiner
David E
DE
Alter
Harvey J
HJ
Lempicki
Richard A
RA
Wood
Brad
B
Yang
Jun
J
Fullmer
Brandie
B
Cortez
Karoll J
KJ
Polis
Michael A
MA
Kottilil
Shyam
S
D000998:Antiviral Agents / Q000627:therapeutic use; D055612:Cytokine-Induced Killer Cells; D005786:Gene Expression Regulation / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D008214:Lymphocytes / Q000502:physiology
D000998:Antiviral Agents; D019409:Interleukin-15