Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules

• Published in: The Journal of experimental medicine Vol. 173; no. 6; pp. 1549 - 1552
• Main Authors: GUY-GRAND, D, MALASSIS-SERIS, M, BRIOTTET, C, VASSALLI, P
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.06.1991; The Rockefeller University Press
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Base Sequence; Biological and medical sciences; Blotting, Northern; Cell Differentiation; Cytoplasmic Granules - ultrastructure; Cytotoxicity, Immunologic; Epithelial Cells; Epithelium - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Graft vs Host Reaction; Granzymes; Immunity, Cellular; Immunobiology; Intestines - cytology; Intestines - immunology; Membrane Glycoproteins; Membrane Proteins - genetics; Mice; Mice, Inbred Strains; Molecular Sequence Data; Oligonucleotide Probes - chemistry; Organs and cells involved in the immune response; Perforin; Pore Forming Cytotoxic Proteins; Serine Endopeptidases - genetics; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; Thymus Gland - immunology; Transcription, Genetic; Cell function; Rodentia; Cytology; Gut; Cell microenvironment; Hybridoma; Cytotoxicity; Epithelium; Cell subpopulation; Vertebrata; Mammalia; Mouse; T-Lymphocyte; Target cell
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.173.6.1549

Mouse gut intraepithelial lymphocytes (IEL), whether thymodependent (CD4+ or CD8 alpha/beta +; TCR-alpha/beta +) or thymoindependent (CD8 alpha/alpha +; TCR-alpha/beta + or -gamma/delta +), all display cytotoxic activity in a "redirected lysis assay" using anti-CD3 or anti-TCR beta or delta chains secreting hybridomas as targets; this is also observed with IEL of germ-free mice, indicating that this activity, which is absent in peripheral T lymphocytes, does not require stimulation by bacterial antigens. Perforin and granzyme transcripts are detectable in unselected gut IEL, in contrast to normal T lymphocytes of peripheral lymphoid organs. Cytological labeling (with [3H]DFP) of IEL smears reveals labeled granules (i.e., containing serine-esterases, presumably granzymes) in all subsets of gut IEL. This indicates that the gut micro-environment has an inductive role on the cytotoxic differentiation of lymphocytes of various origins when they reach the gut wall to become IEL.