A CRITICAL ROLE FOR TRANSFORMING GROWTH-FACTOR-BETA BUT NOT INTERLEUKIN-4 IN THE SUPPRESSION OF T-HELPER TYPE 1-MEDIATED COLITIS BY CD45RB(LOW) CD4(-CELLS() T)

A T helper type 1 (Th1)-mediated colitis with similarities to inflamma tory bowel disease in humans developed in severe combined immunodefici ency mice reconstituted with CD45RB(high) CD4(+) splenic T cells and c ould be prevented by cotransfer of CD45RB(low) CD4(+) T cells. Inhibit ion of this Th1 response by the CD45RB(low) T cell population could be reversed in vivo by an anti-transforming growth factor (TGF) beta ant ibody. Interleukin (IL) 4 was not required for either the differentiat ion or function of protective cells as CD45RB(low) CD4(+) cells from I L-4-deficient mice were fully effective. These results identify a subp opulation of peripheral CD4(+) cells and TGF-beta as critical componen ts of the natural immune regulatory mechanism, which prevents the deve lopment of pathogenic Th1 responses in the gut, and suggests that this immunoregulatory population is distinct from Th2 cells.