| First Author | Meng Z | Year | 2017 |
| Journal | Immunology | Volume | 151 |
| Issue | 1 | Pages | 43-55 |
| PubMed ID | 28092402 | Mgi Jnum | J:249711 |
| Mgi Id | MGI:5924038 | Doi | 10.1111/imm.12712 |
| Citation | Meng Z, et al. (2017) gammadelta T cells are indispensable for interleukin-23-mediated protection against Concanavalin A-induced hepatitis in hepatitis B virus transgenic mice. Immunology 151(1):43-55 |
| abstractText | Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between gammadelta T cells and liver damage in patients with hepatitis B virus (HBV). However, whether gammadelta T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using HBV transgenic (HBs-Tg) and HBs-Tg T-cell receptor-delta-deficient (TCR-delta-/- ) mice, we found that mice genetically deficient in gammadelta T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon-gamma (IFN-gamma) levels and more extensive necrosis. gammadelta T-cell deficiency resulted in elevated IFN-gamma in CD4+ T cells but not in natural killer or natural killer T cells. The depletion of CD4+ T cells and neutralization of IFN-gamma reduced liver damage in HBs-Tg and HBs-Tg-TCR-delta-/- mice to a similar extent. Further investigation revealed that HBs-Tg mice showed an enhanced interleukin-17 (IL-17) signature. The administration of exogenous IL-23 enhanced IL-17A production from Vgamma4 gammadelta T cells and ameliorated liver damage in HBs-Tg mice, but not in HBs-Tg-TCR-delta-/- mice. In summary, our results demonstrated that gammadelta T cells played a protective role in restraining Con A-induced hepatitis by inhibiting IFN-gamma production from CD4+ T cells and are indispensable for IL-23-mediated protection against Con A-induced hepatitis in HBs-Tg mice. These results provided a potential therapeutic approach for treating the hypersensitivity of HBV carriers to biochemical stimulation-induced liver damage. |
