Role of transcription factor T-bet expression by CD4+ cells in gastritis due to Helicobacter pylori in mice.
Gastritis due to Helicobacter pylori is induced by a Th1-mediated response that is CD4 cell and gamma interferon (IFN-gamma) dependent. T-bet is a transcription factor that directs differentiation of and IFN-gamma secretion by CD4+ Th1 T cells. The goal of this study was to use two mouse models to elucidate the role of T-bet in gastritis due to H. pylori. C57BL/6J mice, congenic T-bet knockout (KO) mutants, or congenic SCID (severe, combined immunodeficient) mutants were given live H. pylori by oral inoculation. SCID mice were given CD4+ splenocytes from C57BL/6J or T-bet KO mice by intraperitoneal injection. Twelve or 24 weeks after bacterial inoculation, C57BL/6J mice developed moderate gastritis but T-bet KO mice and SCID mice did not. In contrast, SCID recipients of either C57BL/6J T cells or T-bet KO T cells developed gastritis 4 or 8 weeks after adoptive transfer. In recipients of C57BL/6J CD4+ cells but not recipients of T-bet KO cells, gastritis was associated with a delayed-type hypersensitivity response to H. pylori antigen and elevated gastric and serum IFN-gamma, interleukin 6, and tumor necrosis factor alpha. In spite of the absence of IFN-gamma expression, indicating failure of Th1 differentiation, CD4+ T cells from T-bet KO mice induce gastritis in H. pylori-infected recipient SCID mice. This indicates that Th1-independent mechanisms can cause gastric inflammation and disease due to H. pylori.
Eaton
Kathryn A
KA
University of Michigan, Ann Arbor, Michigan 48109, USA. kateaton@umich.edu
Benson
Lucy H
LH
Haeger
Jennifer
J
Gray
Brian M
BM
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa; D005756:Gastritis / Q000276:immunology* / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors