CD4+CD45RBHi interleukin-4 defective T cells elicit antral gastritis and duodenitis.
We have analyzed the gastrointestinal inflammation which develops following adoptive transfer of IL-4 gene knockout (IL-4(-/-)) CD4(+)CD45RB(Hi) (RB(Hi)) T cells to severe combined immunodeficient (SCID) or to T cell-deficient, T cell receptor beta and delta double knockout (TCR(-/-)) mice. Transfer of IL-4(-/-) RB(Hi) T cells induced a similar type of colitis to that seen in SCID or TCR(-/-) recipients of wild-type (wt) RB(Hi) T cells as reported previously. Interestingly, transfer of both wt and IL-4(-/-) RB(Hi) T cells to TCR(-/-) but not to SCID mice induced inflammation in the gastric mucosa. Notably, TCR(-/-) recipients of IL-4(-/-) RB(Hi) T cells developed a more severe gastritis with erosion, apoptosis of the antral epithelium, and massive infiltration of macrophages. This gastritis was partially dependent on the indigenous microflora. Recipients of both wt and IL-4(-/-) RB(Hi) T cells developed duodenitis with multinuclear giant cells, expansion of mucosal macrophages, and dendritic cells. Full B cell responses were reconstituted in TCR(-/-) recipients of RB(Hi) T cells; however, anti-gastric autoantibodies were not detected. We have now developed and characterized a novel model of chronic gastroduodenitis in mice, which will help in our understanding of the mechanisms involved in chronic inflammation in the upper gastrointestinal tract of humans.
Department of Gastroenterology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. dohi@ri.imcj.go.jp.
Taeko
T
Dohi
Kohtaro
K
Fujihashi
Toshiya
T
Koga
Yuri
Y
Etani
Naoto
N
Yoshino
Yuki I
YI
Kawamura
Jerry R
JR
McGhee
D019264:Adoptive Transfer; D000818:Animals; D029681:Arabidopsis Proteins; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004382:Duodenitis / Q000276:immunology* / Q000473:pathology; D005756:Gastritis / Q000276:immunology* / Q000473:pathology; D015847:Interleukin-4 / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000276:immunology; D017493:Leukocyte Common Antigens; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D011706:Pyloric Antrum / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D029681:Arabidopsis Proteins; D015704:CD4 Antigens; D016207:Cytokines; C484238:PCC1 protein, Arabidopsis; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D017493:Leukocyte Common Antigens