Intra- and intercompartmental movement of gammadelta T cells

TY - JOUR

T1 - Intra- and intercompartmental movement of gammadelta T cells

T2 - intestinal intraepithelial and peripheral gammadelta T cells represent exclusive nonoverlapping populations with distinct migration characteristics

AU - Chennupati, Vijaykumar

AU - Worbs, Tim

AU - Liu, Xiaosun

AU - Malinarich, Frano H

AU - Schmitz, Susanne

AU - Haas, Jan D

AU - Malissen, Bernard

AU - Förster, Reinhold

AU - Prinz, Immo

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Unlike the ∼1% of γδ TCR-positive T cells being regularly present in blood and secondary lymphoid organs (peripheral γδ T cells), ∼50-60% of small intestinal intraepithelial lymphocytes (iIELs) in the mouse express the γδ TCR (γδ iIELs). In this study, we investigated the overlap and exchange of γδ iIELs and γδ T cells found in peripheral secondary lymphoid organs. Using two-photon laser-scanning microscopy, we found γδ T cells within peripheral lymph nodes to be highly motile, whereas γδ iIELs were characterized by a locally confined scanning behavior. Our results implied a strict separation of peripheral γδ T cells and γδ iIELs. Nevertheless, γδ 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 γδ iIELs was very poor. In CCR9-deficient mice, homing of γδ iIELs was impaired, but did not lead to an accumulation of γδ iIEL-like cells in the periphery. Conversely, in situations in which specific γδ iIEL niches were empty, adoptive transfer of isolated γδ iIELs led to a sustained engraftment of transferred γδ iIELs in the intestinal epithelium for at least 100 d. Furthermore, we demonstrated by heterotopic intestinal transplantation experiments that an exchange of γδ iIELs only rarely happens in the steady state of adult mice. We therefore conclude that peripheral versus intestinal intraepithelial γδ T cells are exclusive, nonoverlapping populations that virtually do not exchange with each other.

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

KW - Adoptive Transfer

KW - Animals

KW - Cell Lineage/immunology

KW - Cell Movement/immunology

KW - Cell Separation

KW - Flow Cytometry

KW - Immunity, Mucosal/immunology

KW - Intestinal Mucosa/cytology

KW - Lymph Nodes/cytology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Microscopy, Confocal

KW - Receptors, Antigen, T-Cell, gamma-delta/immunology

KW - T-Lymphocyte Subsets/cytology

KW - T-Lymphocytes/cytology

U2 - 10.4049/jimmunol.1001652

DO - 10.4049/jimmunol.1001652

M3 - SCORING: Journal article

C2 - 20870939

VL - 185

SP - 5160

EP - 5168

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 9

ER -