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.
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.
Guy-Grand
D
D
INSERM U.132, Hôpital Necker-Enfants Malades, Paris, France.
Malassis-Seris
M
M
Briottet
C
C
Vassalli
P
P
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D015870:Gene Expression; D006087:Graft vs Host Reaction; D053804:Granzymes; D007111:Immunity, Cellular; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014158:Transcription, Genetic
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015345:Oligonucleotide Probes; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; D012697:Serine Endopeptidases