A possible involvement of Fas-Fas ligand signaling in the pathogenesis of murine autoimmune gastritis.

Abstract:

BACKGROUND & AIMS:A Th1 clone, II-6, established from an autoimmune gastritis BALB/c mouse that underwent thymectomy 3 days after birth, recognized a 15 mer peptide constructing the alpha subunit of H+, K(+)-adenosine triphosphatase as antigen and induced gastritis in nu/nu mice by adoptive transfer. The aim of this study was to examine the molecular mechanism of target (parietal cells) destruction in either thymectomized or II-6 cell-transferred nu/nu mice. METHODS:Expression of Fas, major histocompatibility complex class II, and intercellular adhesion molecule 1 molecules on the gastric mucosa of these mice were immunohistochemically examined. In situ DNA fragmentation in these thymectomized or nu/nu mice was tested by the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end label (TUNEL) method. Moreover, activity of II-6 cells to induce apoptosis was tested by using the 15 mer peptide-pulsed B lymphoma cells, A20.2J, as the target. RESULTS:A portion of parietal cells in gastritis-bearing thymectomized or nu/nu mice at an early stage expressed Fas, major histocompatibility complex class II, and intercellular adhesion molecule 1 molecules and was TUNEL positive. Fas-ligand message was induced on activated II-6 cells and caused DNA fragmentation of the antigen-pulsed A20.2J cells. CONCLUSIONS:Cognate interaction between Fas antigen on the target and Fas ligand on the effector seems to be one possible mechanism for the target cell destruction in organ-specific autoimmune gastritis.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Nishio A,Katakai T,Oshima C,Kasakura S,Sakai M,Yonehara S,Suda T,Nagata S,Masuda T

doi

10.1016/s0016-5085(96)70063-x

subject

Has Abstract

pub_date

1996-10-01 00:00:00

pages

959-67

issue

4

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(96)70063-X

journal_volume

111

pub_type

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