SummaryMouse gut intraepithelial lymphocytes (IEL) consist mainly (90%) of two populations of CD8+ T cells . One bears heterodimeric ct/0 CD8 chains (Lyt-2+, Lyt-3+), a T cell receptor (TCR) made of ac/(3 chains, and is Thy-1+ ; it represents the progeny of T blasts elicited in Peyer's patches by antigenic stimulation. The other bears homodimeric cx/a CD8+ chains, contains no a chain mRNA, and is mostly Thy-1 -and TCIt-y/S+ or -ci/)3+ ; it is thymo-independent and does not require antigenic stimulation, as shown by its presence: (a) in nude and scid mice; (b) in irradiated and thymectomized mice repopulated by T-depleted bone marrow cells bearing an identifiable marker ; (c) in thymectomized mice treated by injections of monoclonal anti-CD8 antibody, which lead to total depletion of peripheral CD8+ T lymphocytes ; and (d) in germfree mice and in suckling mice . In young nude mice, cx/a CD8 chains, CD3 TCR complexes, and TCR mRNAs (first , y/6) are found on IEL, while they are not detectable on or in peripheral or circulating lymphocytes or bone marrow cells . IEL, in contrast to mature T cells, contain mRNA for the RAG protein, which is required for the rearrangement of TCR and Ig genes. We propose that the gut epithelium (an endoderm derivative, as the thymic epithelium) has an inductive property, attracting progenitors of bone marrow origin, and triggering their TCR rearrangement and cx/u CD8 chains expression, thus giving rise to a T cell population that appears to belong to the same lineage as y/6 thymocytes and to recognize an antigenic repertoire different from that of u/(3 CD8+ IEL.

SummaryMouse gut intraepithelial lymphocytes (IEL), whether thymodependent (CD4+ or CD8 cl/(3+ ; TCR-a/(3 + ) or thymoindependent (CD8 a/a+ ; TCR-ac/R+ or -y/6+), all display cytotoxic activity in a "redirected lysis assay" using anti-CD3 or antiTCR a or 6 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.