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.
Murine gut intraepithelial (IEL) T cell receptor (TCR)-α/β1 lymphocytes bearing CD8α/β or CD8α/α coreceptors have been shown previously to express different oligoclonal TCR β chain repertoires in the same mouse, in agreement with other evidence indicating that these two populations belong to different ontogenic lineages, with only CD8α/β1 IELs being fully thymus dependent. CD8α/β1, but not CD8α/α1, T lymphocytes are also present in the lamina propria. Here, we show that CD8α/β+ lymphocytes from the lamina propria and the epithelium are both oligoclonal, and that they share the same TCR-β clonotypes in the same mouse, as is also the case for CD4+ T cells. Furthermore, identical T cell clones were detected among CD8α/β1 IELs and CD8α/β1 blasts circulating into the thoracic duct (TD) lymph of the same mouse, whereas TD small lymphocytes are polyclonal. These findings must be considered in light of previous observations showing that T blasts, but not small T lymphocytes, circulating in the TD lymph have the capacity of homing into the gut epithelium and lamina propria. These combined observations have interesting implications for our understanding of the recirculation of gut thymus-dependent lymphocytes and their precursors, and of the events leading up to the selection of their restricted TCR repertoire.
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