INTERACTIONS BETWEEN STEM-CELL FACTOR AND C-KIT ARE REQUIRED FOR INTESTINAL IMMUNE-SYSTEM HOMEOSTASIS

Interactions between stem cell factor (SCF) and its receptor, c-Kit, a re important for development of hematopoietic, melanocytes, and germ c ells. T lymphocytes appeared normal in c-Kit (W/W-v) or SCF (SI/SId) m utant mice, except for those residing within the intestinal epithelium , the intraepithelial lymphocytes (IEL). Normally, IEL are composed of equal numbers of cells with alpha beta or gamma delta T cell receptor s. In mutant mice, beginning at 6-8 weeks of age, the number of gamma delta IEL decreased, whereas alpha beta IEL increased. The latter was due largely to an increased CD4(+)CD8(+) TCR alpha beta subset, sugges ting that these cells may be intermediates in the alpha beta IEL linea ge. c-Kit or SCF was expressed by IEL or intestinal epithelial cells, respectively, indicating a potential for direct intercellular interact ion. This possibility was supported by reconstitution studies that dem onstrated that c-Kit mutations directly affected IEL. Thus, SCF-c-Kit interactions are important for homeostasis of the intestinal immune co mpartment.