A possible involvement of Fas-Fas ligand signaling in the pathogenesis of murine autoimmune gastritis.
OBJECTIVE
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.
Nishio
A
A
Institute for Immunology, Faculty of Medicine, Kyoto University, Japan.
Katakai
T
T
Oshima
C
C
Kasakura
S
S
Sakai
M
M
Yonehara
S
S
Suda
T
T
Nagata
S
S
Masuda
T
T
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005756:Gastritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1