Intra- and Intercompartmental Movement of γδ T Cells: Intestinal Intraepithelial and Peripheral γδ T Cells Represent Exclusive Nonoverlapping Populations with Distinct Migration Characteristics

Unlike the similar to 1% of gamma delta TCR-positive T cells being regularly present in blood and secondary lymphoid organs (peripheral gamma delta T cells), similar to 50-60% of small intestinal intraepithelial lymphocytes (iIELs) in the mouse express the gamma delta TCR (gamma delta iIELs). In this study, we investigated the overlap and exchange of gamma delta iIELs and gamma delta T cells found in peripheral secondary lymphoid organs. Using two-photon laser-scanning microscopy, we found gamma delta T cells within peripheral lymph nodes to be highly motile, whereas gamma delta iIELs were characterized by a locally confined scanning behavior. Our results implied a strict separation of peripheral gamma delta T cells and gamma delta iIELs. Nevertheless, gamma delta iIELs could be efficiently regenerated from bone marrow-derived precursors in irradiated or T cell-deficient adult mice. However, outside the intestinal epithelium, survival of gamma delta iIELs was very poor. In CCR9-deficient mice, homing of gamma delta iIELs was impaired, but did not lead to an accumulation of gamma delta iIEL-like cells in the periphery. Conversely, in situations in which specific gamma delta iIEL niches were empty, adoptive transfer of isolated gamma delta iIELs led to a sustained engraftment of transferred gamma delta iIELs in the intestinal epithelium for at least 100 d. Furthermore, we demonstrated by heterotopic intestinal transplantation experiments that an exchange of gamma delta iIELs only rarely happens in the steady state of adult mice. We therefore conclude that peripheral versus intestinal intraepithelial gamma delta T cells are exclusive, nonoverlapping populations that virtually do not exchange with each other. The Journal of Immunology, 2010, 185: 5160-5168.