• CD8αα+-IEL;
  • γδ-IEL;
  • αβ-IEL;
  • extrathymic development of IEL;
  • cryptopatches

Summary:  The alimentary tract has an epithelial layer, consisting mainly of intestinal epithelial cells (IECs), that is exposed to the exterior world through the intestinal lumen. The IEC layer contains many intestinal intraepithelial T cells (IELs), and the total number of IELs constitutes the largest population in the peripheral T-cell pool. Virtually all γδ-IELs and many αβ-IELs in the mouse small intestine are known to express CD8αα homodimers. A wide range of evidence that supports extrathymic development of these CD8αα+ IELs has been collected. In addition, while several studies identified cells with precursor T-cell phenotypes within the gut epithelium, how these precursors, which are dispersed along the length of the intestine, develop into γδ-IELs and/or αβ-IELs has not been clarified. The identification of lymphoid cell aggregations named ‘cryptopatches’ (CPs) in the intestinal crypt lamina propria of mice as sites rich in T-cell precursors in 1996 by our research group, however, provided evidence for a central site, whereby precursor IELs could give rise to T-cell receptor-bearing IELs. In this review, we discuss the development of IELs in the intestinal mucosa and examine the possibility that CPs serve as a production site of extrathymic IELs.