CYTOTOXIC DIFFERENTIATION OF MOUSE GUT THYMODEPENDENT AND INDEPENDENT INTRAEPITHELIAL LYMPHOCYTES-T 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 [H-3]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.