BROWSE

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Author

Do, Yoonkyung
DC-based Immune System & Immunotherapy (DISNI) Lab
Research Interests
  • Study on various subsets of dendritic cells and their immunological functions

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CD44-deficient mice exhibit enhanced hepatitis after concanavalin a injection: Evidence for involvement of CD44 in activation-induced cell death

Cited 77 times inthomson ciCited 82 times inthomson ci
Title
CD44-deficient mice exhibit enhanced hepatitis after concanavalin a injection: Evidence for involvement of CD44 in activation-induced cell death
Author
Chen, DWMcKallip, RJZeytun, ADo, YoonkyungLombard, CRobertson, JLMak, TWNagarkatti, PSNagarkatti, M
Keywords
CYTOKINE MESSENGER-RNA; A-INDUCED HEPATITIS; T-CELLS; CYTOLYTIC ACTIVITY; LIVER-INJURY; IFN-GAMMA; APOPTOSIS; LYMPHOCYTES; EXPRESSION; SUPPRESSION
Issue Date
200105
Publisher
AMER ASSOC IMMUNOLOGISTS
Citation
JOURNAL OF IMMUNOLOGY, v.166, no.10, pp.5889 - 5897
Abstract
Administration of Con A induces severe injury to hepatocytes in mice and is considered to be a model for human hepatitis. In the current study, we investigated the role of CD44 in Con A-induced hepatitis. Intravenous administration of Con A (20 mg(kg) caused 100% mortality in C57BL/6 CD44-knockout (KO) mice, although it was not lethal in C57BL/6 CD44 wild-type (WT) mice. Administration of lower doses of Con A (12 mg/kg body weight) into CD44 WT mice induced hepatitis as evident from increased plasma aspartate aminotransferase levels accompanied by active infiltration of mononuclear cells and neutrophils, and significant induction of apoptosis in the liver. Interestingly, CD44 KO mice injected with similar doses of Con A exhibited more severe acute suppurative hepatitis. Transfer of spleen cells from Con A-injected CD44 KO mice into CD44 WT mice induced higher levels of hepatitis when compared with transfer of similar cells from CD44 WT mice into CD44 WT mice. The increased hepatitis seen in CD44 KO mice was accompanied by increased production of cytokines such as TNF-alpha, IL-2 and IFN-gamma, but not Fas or Fas ligand. The increased susceptibility of CD44 KO mice to hepatitis correlated with the observation that T cells from CD44 KO mice were more resistant to activation-induced cell death when compared with the CD44 WT mice. Together, these data demonstrate that activated T cells use CD44 to undergo apoptosis, and dysregulation in this pathway could lead to increased pathogenesis in a number of diseases, including hepatitis.
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ISSN
0022-1767
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