Proliferation and apoptosis of lamina propria CD4+ T cells from scid mice with inflammatory bowel disease

Eur J Immunol. 1998 Nov;28(11):3655-63. doi: 10.1002/(SICI)1521-4141(199811)28:11<3655::AID-IMMU3655>3.0.CO;2-9.

Abstract

Scid mice transplanted with low numbers of syngeneic CD4+ T cells, develop a chronic and lethal inflammatory bowel disease (IBD) within 4-6 months. We have used in vivo 5-bromo2-deoxy-uridine (BrdU) labeling to assess the proliferation of lamina propria-derived CD4+ T cells in diseased scid mice. The hourly rate of renewal of colonic lamina propria CD4+ T cells in diseased mice was 7% compared with 1.5% in normal BALB/c control mice. Transplantation of scid mice with in vitro activated CD4+ T cells accelerated the disease onset and development in a cell dose-dependent fashion when compared with non-activated CD4+ T cells. In pulse-chase experiments it was shown that BrdU-labeled cells disappeared rapidly from the lamina propria of diseased mice. DNA analysis revealed that this was due to the presence of nearly four times as many apoptotic CD4+ T cells in diseased than in control mice. Further analyses showed that the apoptotic lamina propria CD4+ T cells were derived from cells having entered the cell cycle within the previous 8 h. These data clearly demonstrate that vigorous CD4+ T cell proliferation and death are involved throughout the course of IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Bromodeoxyuridine / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Inflammatory Bowel Diseases / immunology*
  • Intestinal Mucosa / immunology*
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Rats

Substances

  • Bromodeoxyuridine