PROLIFERATION AND APOPTOSIS OF LAMINA PROPRIA CD4(-CELLS FROM SCID MICE WITH INFLAMMATORY BOWEL-DISEASE() T)

Scid mice transplanted with low numbers of syngeneic CD4(+) T cells, d evelop a chronic and lethal inflammatory bower disease (IBD) within 4- 6 months. We have used in vivo 5-bromo-2-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 pr opria CD4(+) T cells in diseased mice was 7 % compared with 1.5 % in n ormal 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. D NA analysis revealed that this was due to the presence of nearly four times as many apoptotic CD4(+) T cells in diseased than in control mic e. 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 c ell proliferation and death are involved throughout the course of IBD.