New gut associated lymphoid tissue “cryptopatches” breed murine intestinal intraepithelial T cell precursors

Abstract

Numerous mouse intraepithelial T cells (IEL) bearing either TCR-αΒ or TCR-γδ have been shown to develop somewhere in the intestinal mucosa without passing through the thymus. However, just where these T cells develop has been much less clear and has remained an open question to date. In an effort to investigate this issue, we carried out immunohistochemical study on the murine gastrointestinal tract and identified numerous tiny lymphoid tissues (~1,650 tissues/intestine) in the cryptal region of the small and large intestinal mucosa except for the stomach in which clusters of c-kit⁺ IL-7R⁺ Thy1⁺ lympho-hemopoietic progenitors accumulated (cryptopatches). The cryptopatch cells isolated from the small intestine, which were c-kit positive (c-kit⁺) but lineage marker negative (Lin), gave rise to TCR-αΒ and TCR-γδ IELs following in vivo transfer or tissue engraftment into 2 Gy-irradiated severe combined immunodeficient mice. In contrast, cells isolated from Peyer’s patches and mesenteric lymph nodes, which belong in the same intestinal immune compartment but lack c-kit⁺Lin^- cells, failed to do so. These results in conjunction with the findings of electron microscopic analysis provide direct evidence of a local intestinal T cell precursor that develops in the cryptopatches.