Altered enteroendocrine cell expression in T cell receptor alpha chain knock-out mice

Mice lacking T cell receptor alpha chain (TCR alpha(-/-)) develop inflammat ion of the colon. We have examined the effect of this inflammation on the c olonic epithelium by studying markers of epithelial cuff, enteroendocrine, and immune cell differentiation. Using immunohistochemical techniques, colo ns were compared in normal C57/BL6 and murine TCR alpha(-/-) mice aged 2 an d 3 weeks and 3-11 months. TCR alpha(-/-) mice aged 3-11 months had histolo gic evidence of inflammation with increased expression of CD45, CD4+, CD8+, and B220 + cells and a decrease in expression of IgA+ cells. There was a d ecrease in the number of cholecystokinin, serotonin, and neurotensin entero endocrine expressing cells in the colon of TCR alpha(-/-) mice. These chang es were not present in 2-3-week-old suckling/weaning mice. In contrast, pep tide tyrosine tyrosine (PYY), glucagon-like peptide-1, and gastrin expressi on did not change and small intestinal enteroendocrine cells remained unalt ered. The change in colonic enteroendocrine cell expression appears to be a specific response, since only a subset of these cells was altered, and the epithelium was intact by histologic analysis. The absence of functional T cells in TCR alpha(-/-) colon has a marked effect on differentiation of a s pecific subpopulation of enteroendocrine cells, prior to loss of integrity of the epithelium. (C) 2000 Wiley-Liss, Inc.