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.
Dohi
Taeko
T
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.
Fujihashi
Kohtaro
K
Koga
Toshiya
T
Etani
Yuri
Y
Yoshino
Naoto
N
Kawamura
Yuki I
YI
McGhee
Jerry R
JR
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