Platelets mediate cytotoxic T lymphocyte-induced liver damage.
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.
Iannacone
Matteo
M
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Sitia
Giovanni
G
Isogawa
Masanori
M
Marchese
Patrizia
P
Castro
Maria G
MG
Lowenstein
Pedro R
PR
Chisari
Francis V
FV
Ruggeri
Zaverio M
ZM
Guidotti
Luca G
LG
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002452:Cell Count; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015539:Platelet Activation; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*