Contribution of CD1d-unrestricted hepatic DX5+ NKT cells to liver injury in Plasmodium berghei-parasitized erythrocyte-injected mice

Int Immunol. 2004 Jun;16(6):787-98. doi: 10.1093/intimm/dxh080. Epub 2004 Apr 13.


Inoculation with erythrocytes infected with Plasmodium berghei, a protozoan causing mouse lethal malaria, induces liver injury in mice, although the parasite cannot invade host hepatocytes at this infectious stage. As previously reported, hepatic infiltrates participate in this liver injury by exerting their perforin-dependent killing action. Here, we have investigated the cellular mechanisms underlying P. berghei-induced incidental liver injury. Hepatic lymphocytes from P. berghei-infected mice killed normal hepatocytes, but not ConA-induced lymphoblasts. Furthermore, the hepatic lymphocytes from infected C57BL/6 mice displayed cytotoxicity against hepatocytes from C57BL/6 and BALB/c mice, indicating MHC-unrestricted hepatocytotoxicity by these hepatic lymphocytes. NK cells were not involved in this hepatocytotoxicity. However, DX5+ cells sorted from the liver of infected CD1d-deficient mice killed normal hepatocytes, indicating that CD1d-independent DX5+ T cells are the effector cells. The hepatocytotoxicity of these hepatic DX5+ T cells did not require TCR engagement. These findings indicate that hepatic CD1d-independent DX5+ T cells play a critical role in P. berghei-induced liver injury. Our studies may have general implications for tissue injuries that are caused by 'bystander killing' or other poorly defined cell-mediated killing mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / analysis
  • Animals
  • Antigens, CD1 / metabolism*
  • Antigens, CD1d
  • Cytotoxicity, Immunologic / immunology
  • Erythrocytes / parasitology
  • Female
  • Hepatitis, Animal / immunology*
  • Hepatitis, Animal / parasitology*
  • Hepatitis, Animal / pathology
  • Hepatocytes / immunology
  • Hepatocytes / parasitology
  • Hepatocytes / pathology
  • Injections
  • Interleukin-12 / analysis
  • Killer Cells, Natural / immunology*
  • Liver / immunology*
  • Liver / parasitology
  • Liver / pathology
  • Malaria / immunology*
  • Malaria / parasitology
  • Malaria / pathology
  • Mice
  • Mice, Inbred Strains
  • Parasitemia / enzymology
  • Parasitemia / immunology
  • Plasmodium berghei*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocyte Subsets / immunology*


  • Antigens, CD1
  • Antigens, CD1d
  • Receptors, Antigen, T-Cell
  • Interleukin-12
  • Alanine Transaminase