Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis.
OBJECTIVE
Murine autoimmune gastritis, induced by day-3 thymectomy, is characterized by cellular infiltrates and circulating autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. The aim of this study was to analyze the cellular infiltrates and cytokines in autoimmune gastritis.


METHODS
Stomachs and blood samples from day-3 thymectomized BALB/c mice were obtained from 2 to 12 weeks after thymectomy for analysis.


RESULTS
At 4 weeks, the gastritic infiltrates were composed of macrophages and CD4+ T cells, accompanied by major histocompatibility complex class II expression on gastric epithelial cells. Mucosal B cells, scant at 4 weeks, were abundant at 8 weeks, coincident with the peaking of autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. CD8+ T cells increased marginally during the 12 weeks. Mononuclear cells from diseased stomachs transferred gastritis to nu/nu recipients. At 4 weeks, interleukins 2, 3, 5, 6, and 10; interferon gamma; tumor necrosis factor alpha; and granulocyte-macrophage colony-stimulating factor were detected in gastritic mucosa, but interleukin 4 was not.


CONCLUSIONS
The early lesion of autoimmune gastritis is composed of macrophages and CD4+ T cells with major histocompatibility complex class II expression in gastric epithelial cells. Autoantibody production is a late event. Our results are consistent with a lesion mediated by CD4+ T cells producing a mix of Th1- and Th2-type cytokines.
Martinelli
T M
TM
Department of Pathology and Immunology, Monash University Medical School, Alfred Hospital, Melbourne, Victoria, Australia.
van Driel
I R
IR
Alderuccio
F
F
Gleeson
P A
PA
Toh
B H
BH
D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007150:Immunohistochemistry; D016131:Lymphocyte Subsets / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009000:Monocytes / Q000502:physiology*; D010641:Phenotype
D001323:Autoantibodies; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D017506:H(+)-K(+)-Exchanging ATPase