Polyclonal expansion of adoptively transferred CD4+ alpha beta T cells in the colonic lamina propria of scid mice with colitis.
The adoptive transfer of low numbers of peripheral, non-fractionated CD4+ alpha beta T cells into histocompatible, severely immunodeficient (scid) hosts induces a colitis. This disease developed in C.B-17 scid/scid hosts after the injection of 10(5) CD4+ T cells purified from different peripheral lymphoid organs of immunocompetent C.B.-17 +/+ or BALB/cdm2 donor mice. Irrespective of their tissue origin, transferred CD4+ T cells selectively repopulated the scid host with gut-seeking CD4+ T cells. A chronic inflammatory bowel disease (IBD) developed as polyclonal populations of mucosa-seeking memory/effector CD4+ T cells accumulated in the gut lamina propria and epithelial layer of the adoptive host. The manifestation of colitis in the scid host correlated with the in situ polyclonal activation and expansion of adoptively transferred CD4+ T cells in the colonic lamina propria. Attempts were unsuccessful to select in vivo an oligoclonal CD4+ T cell population with an enhanced IBD-inducing potential by repeatedly reinjecting 10(5) donor-type CD4+ T cells from the colonic lamina propria of transplanted scid mice with an early and severe IBD into new scid hosts. The data indicate that the preferential repopulation of gut-associated lymphoid tissues with immunocompetent CD4+ T cells, and their polyclonal activation and in situ expansion in the lamina propria of the histocompatible, immunodeficient host are critical events in the pathogenesis of an IBD in this model.
Rudolphi
A
A
Institute for Medical Microbiology and Immunology, University of Ulm, Germany.
Bonhagen
K
K
Reimann
J
J
D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D002460:Cell Line; D003092:Colitis / Q000209:etiology / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D005810:Multigene Family / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta