Massive upregulation of the fas ligand in lpr and gld mice: Implications for fas regulation and the graft-versus-host disease-like wasting syndrome

Jia Li Chu, Paula Ramos, Adam Rosendorff, Janko Nikolć-Zugić, Elizabeth Lacy, Akio Matsuzawa, Keith B. Elkon

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CDS-) phenotype. Previous studies have shown that these abnormal cells are capable of inducing redirected lysis of certain Fc receptor-positive target cells. Since the Fas ligand (FasL) has recently been shown to be partly responsible for T cell-mediated cytotoxicity, lymph node cells from lpr and gld mice were examined for the expression of FasL mKNA. Northern blot analysis revealed that lymph node cells obtained from Ipr and gld mice had a striking increase in the level of expression of FasL mRNA predominantly due to expression in the DN T cells. Furthermore, Ipr, but not g/d lymph node cells killed the B cell line, A20, in a Fas-dependent manner. These findings indicate that Fas mutations result in a massive upregulation of FasL which, most likely, results from repetitive exposure to (self) antigen. This phenomenon could explain the Ipr-induced wasting syndrome observed when lpr bone marrow-. derived cells are adoptively transferred to wild-type recipients.

Original languageEnglish (US)
Pages (from-to)393-398
Number of pages6
JournalJournal of Experimental Medicine
Volume181
Issue number1
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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