| 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. © 1995, Rockefeller University Press., All rights reserved. |
| Keywords: |
mutation; nonhuman; flow cytometry; t lymphocyte; animal cell; mouse; phenotype; animal; mice; animal tissue; gene expression; animal model; mice, mutant strains; age factors; dna; molecular sequence data; antigen; messenger rna; rna, messenger; membrane glycoproteins; ligand; graft versus host reaction; adoptive transfer; base sequence; fc receptor; cytotoxicity, immunologic; cachexia; t-lymphocyte subsets; dna primers; autoimmune diseases; graft vs host disease; lymphadenopathy; antigens, surface; northern blotting; cell mediated cytotoxicity; mice, inbred c3h; lymphatic diseases; antigens, cd95; lymph node cell; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; support, u.s. gov't, non-p.h.s.
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