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Updated: Jul 8, 2026

Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic
Matteo Iannacone1, Giovanni Sitia, Masanori Isogawa
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract:
We found that mice infected with different isolates of lymphocytic choriomeningitis virus (LCMV) develop a mild hemorrhagic anemia, which becomes severe and eventually lethal in animals depleted of platelets or lacking integrin beta3. Lethal hemorrhagic anemia is mediated by virus-induced IFN-alpha/beta that causes platelet dysfunction, mucocutaneous blood loss and suppression of erythropoiesis. In addition to the life-threatening hemorrhagic anemia, platelet-depleted mice fail to mount an efficient cytotoxic T lymphocyte (CTL) response and cannot clear LCMV. Transfusion of functional platelets into these animals reduces hemorrhage, prevents death and restores CTL-induced viral clearance in a manner partially dependent on CD40 ligand (CD40L). These results indicate that, upon activation, platelets expressing integrin beta3 and CD40L are required for protecting the host against the induction of an IFN-alpha/beta-dependent lethal hemorrhagic diathesis and for clearing LCMV infection through CTLs.
Insights
Platelets are crucial for preventing lethal hemorrhagic anemia and clearing lymphocytic choriomeningitis virus (LCMV) infection in mice. Their function, mediated by integrin beta3 and CD40L, is vital for host defense against virus-induced IFN-alpha/beta.
Area of Science:
- Immunology
- Virology
- Hematology
Background:
- Lymphocytic choriomeningitis virus (LCMV) infection can lead to hemorrhagic anemia.
- Platelets and integrin beta3 play a role in regulating bleeding and immune responses.
- IFN-alpha/beta signaling is implicated in viral pathogenesis.
Purpose of the Study:
- To investigate the role of platelets and integrin beta3 in LCMV-induced hemorrhagic anemia.
- To elucidate the mechanisms by which platelets protect against lethal anemia and viral clearance.
Main Methods:
- Induction of LCMV infection in mice.
- Experimental depletion of platelets and genetic modification to lack integrin beta3.
- Assessment of hemorrhagic anemia, IFN-alpha/beta levels, erythropoiesis, and cytotoxic T lymphocyte (CTL) responses.
- Platelet transfusion experiments.
Main Results:
- Mice lacking platelets or integrin beta3 developed severe, lethal hemorrhagic anemia.
- Virus-induced IFN-alpha/beta caused platelet dysfunction, bleeding, and suppressed red blood cell production.
- Platelet depletion impaired CTL responses and viral clearance.
- Platelet transfusion reduced hemorrhage, prevented death, and restored CTL-mediated viral clearance.
Conclusions:
- Platelets expressing integrin beta3 are essential for preventing lethal hemorrhagic anemia induced by LCMV.
- Platelets are required for effective CTL-mediated viral clearance.
- Integrin beta3 and CD40L on activated platelets protect against IFN-alpha/beta-dependent hemorrhagic diathesis and facilitate viral clearance.
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