POLYCLONAL EXPANSION OF ADOPTIVELY TRANSFERRED CD4(-BETA T-CELLS IN THE COLONIC LAMINA PROPRIA OF SCID MICE WITH COLITIS() ALPHA)

The adoptive transfer of low numbers of peripheral, non-fractionated C D4(+) alpha beta T cells into histocompatible, severely immunodeficien t (scid) hosts induces a colitis. This disease developed in C.B-17 sci d/scid hosts after the injection of 10(5) CD4(+) T cells purified from different peripheral lymphoid organs of immunocompetent C.B-17 +/+ or BALB/c(dm2) donor mice. Irrespective of their tissue origin, transfer red CD4(+) T cells selectively repopulated the scid host with gut-seek ing CD4(+) T cells. A chronic inflammatory bowel disease (IBD) develop ed 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 corre lated with the in situ polyclonal activation and expansion of adoptive ly transferred CD4(-) T cells in the colonic lamina propria. Attempts were unsuccessful to select in vivo an oligoclonal CD4(-) T cell popul ation with an enhanced IBD-inducing potential by repeatedly reinjectin g 10(5) donor-type CD4(+) T cells from the colonic lamina propria of t ransplanted scid mice with an early and severe IBD into new scid hosts . The data indicate that the preferential repopulation of gut-associat ed lymphoid tissues with immunocompetent CD4(+) T cells, and their pol yclonal activation and in situ expansion in the lamina propria of the histocompatible. immunodeficient host are critical events in the patho genesis of an IBD in this model.