Cytotoxic reactivity of gut lamina propria CD4+ alpha beta T cells in SCID mice with colitis.
Polyclonal, mucosa-seeking memory/effector CD4+ T cells containing a large fraction of blasts activated in situ accumulate in the gut lamina propria of severe-combined immunodeficient (SCID) mice developing colitis after CD4+ T cell transplantation. CD4+ T cells isolated from different repopulated lymphoid tissues of transplanted SCID mice proliferate in vitro in the presence of interleukin (IL)-2 + IL-7. CD3 ligation enhances this cytokine-supported proliferation in CD4+ T cells from the spleen and the mesenteric lymph node of transplanted SCID mice; CD3 ligation suppresses the cytokine-supported proliferation in CD4+ T cells from the gut lamina propria in a cell density- and dose-dependent manner. Almost all CD4+ T cells from repopulated lymphoid tissues of transplanted SCID mice express CD95 (Fas) on the cell surface, and a large fraction of CD4+ T cells from the gut lamina propria of transplanted SCID mice express the Fas ligand on the surface. Gut lamina propria CD4+ T cells show Fas-dependent cytotoxicity. A large fraction of gut lamina propria CD4+ T cells that infiltrate the inflamed colon in transplanted SCID mice are activated in situ and many CD4+ T cells are apoptotic. Hence, a large fraction of colitis-inducing CD4+ T cells undergo activation-induced cell death in situ and can damage other cells through Fas-dependent cytotoxicity.
Bonhagen
K
K
Institute for Medical Microbiology and Immunology, University of Ulm, Germany.
Thoma
S
S
Bland
P
P
Bregenholt
S
S
Rudolphi
A
A
Claesson
M H
MH
Reimann
J
J
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001485:Basement Membrane / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003092:Colitis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009928:Organ Specificity / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D019014:fas Receptor / Q000494:pharmacology
D017252:CD3 Complex; D007376:Interleukin-2; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor