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IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B
Jean Publicover, … , Stewart Cooper, Jody L. Baron
Jean Publicover, … , Stewart Cooper, Jody L. Baron
Published February 14, 2011
Citation Information: J Clin Invest. 2011;121(3):1154-1162. https://doi.org/10.1172/JCI44198.
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Research Article Virology Article has an altmetric score of 5

IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B

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Abstract

HBV is a noncytopathic hepadnavirus and major human pathogen that causes immune-mediated acute and chronic hepatitis. The immune response to HBV antigens is age dependent: viral clearance occurs in most adults, while neonates and children usually develop chronic infection and liver disease. Here, we characterize an animal model for HBV infection that recapitulates the key differences in viral clearance between early life and adulthood and find that IL-21 may be part of an effective primary hepatic immune response to HBV. In our model, adult mice showed higher HBV-dependent IL-21 production in liver, compared with that of young mice. Conversely, absence of the IL-21 receptor in adult mice resulted in antigen persistence akin to that of young mice. In humans, levels of IL-21 transcripts were greatly increased in blood samples from acutely infected adults who clear the virus. These observations suggest a different model for the dichotomous, age-dependent outcome of HBV infection in humans, in which decreased IL-21 production in younger patients may hinder generation of crucial CD8+ T and B cell responses. These findings carry implications for therapeutic augmentation of immune responses to HBV and potentially other persistent liver viruses.

Authors

Jean Publicover, Amanda Goodsell, Stephen Nishimura, Silvia Vilarinho, Zhi-en Wang, Lia Avanesyan, Rosanne Spolski, Warren J. Leonard, Stewart Cooper, Jody L. Baron

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Figure 2

Transfer of adult splenocytes into young and adult HBVtgRag mice results in a difference in HBsAg clearance and HBsAb responses.

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Transfer of adult splenocytes into young and adult HBVtgRag mice results...
Depiction of (A and B) the percentage of mice with detectable circulating HBsAg and (C and D) plasma HBsAb titer in young and adult (A and C) HBVEnvRag or (B and D) HBVRplRag mice after adoptive transfer of adult wild-type C57BL/6 mouse splenocytes. Error bars show mean ± SEM where N ≥ 5 mice. (E) Presence of HBcAb in plasma of adult or young HBVRplRag mice after adoptive transfer of adult, wild-type C57BL/6 mouse splenocytes (n = 4 mice). Statistical significance was determined using the unpaired 2-tailed t test. Data are representative of at least 3 separate experiments.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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