Induction of wasting disease in SCID mice by the transfer of normal CD4+/CD45RBhi T cells and the regulation of this autoreactivity by CD4+/CD45RBlo T cells.
SCID mice injected with coisogenic CD4+/CD45RBhi lymph node T cells from normal donors develop a wasting disease that is due to hyperplasia of the intestinal epithelium. SCID mice injected with purified lymph node CD4+ T cells or CD4+/CD45RBlo T cells do not develop the disease. In addition, mixture of the CD4+/CD45RBlo T cells with equal numbers of CD4+/CD45RBhi T cells inhibits the development of disease. SCID mice that were reconstituted with CD45RBhi T cells with active disease were treated with oral antibiotics and this ameliorated the symptoms, suggesting a role of the gut bacterial flora in the development of disease. Attempts were made to accelerate or inhibit disease by chronically administering cytokines to the mice. Neither IL2 nor IL4 were effective in altering the course of disease development when given in doses known to be effective in other in vivo models. Thus, the regulation of the reactivity seen in these SCID mice may involve as yet unappreciated mechanisms.
Morrissey
P J
PJ
Immunex Research and Development Corporation, Seattle, WA 98101, USA.
Charrier
K
K
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D001414:Bacitracin / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003967:Diarrhea / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000628:therapy; D006801:Humans; D006965:Hyperplasia; D015212:Inflammatory Bowel Diseases; D007376:Interleukin-2 / Q000008:administration & dosage; D015847:Interleukin-4 / Q000008:administration & dosage; D007420:Intestine, Large / Q000276:immunology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID; D013307:Streptomycin / Q000627:therapeutic use; D015431:Weight Loss
D007376:Interleukin-2; D001414:Bacitracin; D015847:Interleukin-4; D017493:Leukocyte Common Antigens; D013307:Streptomycin