Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 11 (11), 1167-9

Platelets Mediate Cytotoxic T Lymphocyte-Induced Liver Damage

Affiliations

Platelets Mediate Cytotoxic T Lymphocyte-Induced Liver Damage

Matteo Iannacone et al. Nat Med.

Abstract

We found that platelet depletion reduces intrahepatic accumulation of virus-specific cytotoxic T lymphocytes (CTLs) and organ damage in mouse models of acute viral hepatitis. Transfusion of normal but not activation-blocked platelets in platelet-depleted mice restored accumulation of CTLs and severity of disease. In contrast, anticoagulant treatment that prevented intrahepatic fibrin deposition without reducing platelet counts did not avert liver injury. Thus, activated platelets contribute to CTL-mediated liver immunopathology independently of procoagulant function.

Conflict of interest statement

COMPETING INTERESTS STATEMENT

The authors declare that they have no competing financial interests.

Figures

Figure 1
Figure 1
Activated platelets enhance intrahepatic accumulation of CTLs and severity of liver disease in HBV transgenic mice independently of fibrin deposition. Histological analysis of representative HBV transgenic mice injected with either irrelevant antibody (α-Irr; a) or antibody against mouse GPIbα (α-PLT; b) and killed 2 d after transfer of HBV-specific CTLs. Apoptotic hepatocytes are indicated by arrowheads. Scale bars, 50 μm. (c) Mean sALT activity (U/L ± s.d.) measured at the indicated days after CTL transfer in groups of mice (n = 6) that received α-Irr (open triangles), α-PLT (filled squares) or NaCl (gray circles). (d) Absolute number (mean ± s.d.) and (e) in vitro cytotoxicity (mean ± s.d. at different effector-to-target (E:T) ratios) of intrahepatic HBV-specific CTLs recovered from the same mice. (f) sALT values (mean ± s.d.) measured at the time of autopsy (day 1 after CTL transfer) in groups (n = 4) of HBV transgenic mice injected either with α-Irr (white bars) or α-PLT (black, red and blue bars) 24 h before injection of HBV-specific CTLs. Four hours after CTL transfer, one group (red bars) also received TKK-PLTs and one group (blue bars) received TKK-PLTs pretreated with PGE1. Mice receiving NaCl (dark gray bars) or α-PLT and TKK-PLTs but no CTLs (light gray bars) served as controls. (g) Immunohistochemical analysis of fibrin in the liver of representative HBV transgenic mice treated with warfarin (right) or left untreated (left) and killed at day 1 after CTL transfer. Insets show mean sALT levels at the time of autopsy. Scale bars, 150 μm.
Figure 2
Figure 2
Platelet depletion ameliorates liver disease in adenovirus-infected mice and reduces the intrahepatic accumulation of virus-specific CTLs. Histological analysis of representative lacZ-immunized C57BL/6J mice injected with either α-Irr (a) or α-PLT (b) and killed 4 d after RAd35 infection. Scale bars, 150 μm. (c) Mean sALT activity (U/L ± s.d.) measured at the indicated days after RAd35 infection in mice that received α-Irr (open triangles), α-PLT (filled squares) or NaCl (gray circles). (d) Absolute number (mean ± s.d.) of intrahepatic lacZ-specific CTLs recovered from the same mice killed at days 3, 4 and 5 after RAd35 infection. (e) Total hepatic RNA derived from the same mice was analyzed for the expression of IFN-γ by RNAse protection assay. (f) The same total hepatic RNA was analyzed for lacZ RNA (day 5 after RAd35) by northern blot (lower part) and quantified by phosphorimaging analysis (upper part). (g) Fresh frozen liver sections from mice killed at day 5 after RAd35 infection were stained for β-galactosidase activity, and the mean percentage of lacZ+ cells in each section is indicated. Scale bars, 300 μm.

Similar articles

See all similar articles

Cited by 94 PubMed Central articles

See all "Cited by" articles

Publication types

LinkOut - more resources

Feedback