TY - JOUR
T1 - Massive upregulation of the Fas ligand in lpr and gld mice
T2 - Implications for Fas regulation and the graft-versus-host disease-like wasting syndrome
AU - Chu, Jia Li
AU - Ramos, Paula
AU - Rosendorff, Adam
AU - Nikolić-Žugić, Janko
AU - Lacy, Elizabeth
AU - Matsuzawa, Akio
AU - Elkon, Keith B.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CD8-) 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 mRNA. Northern blot analysis revealed that lymph node cells obtained from lpr 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, lpr, but not gld lymph node cells killed the B cell line, A20, in a Fas-dependent manner. These findings indicate that Fas mutations result in a massive up-regulation 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.
AB - Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CD8-) 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 mRNA. Northern blot analysis revealed that lymph node cells obtained from lpr 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, lpr, but not gld lymph node cells killed the B cell line, A20, in a Fas-dependent manner. These findings indicate that Fas mutations result in a massive up-regulation 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.
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U2 - 10.1084/jem.181.1.393
DO - 10.1084/jem.181.1.393
M3 - Article
C2 - 7528774
AN - SCOPUS:0028928654
SN - 0022-1007
VL - 181
SP - 393
EP - 398
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -