DIFFERENT USE OF T-CELL RECEPTOR TRANSDUCING MODULES IN 2 POPULATIONSOF GUT INTRAEPITHELIAL LYMPHOCYTES ARE RELATED TO DISTINCT PATHWAYS OF T-CELL DIFFERENTIATION

Most gut intraepithelial cells (IEL) of the mouse are T cells that bea r CD8 molecules, present either as alpha-beta chain heterodimers (CD8 beta(+)) or as alpha chain homodimers (CD8 beta(-)). All CD8 beta(+) I EL bear alpha/beta T cell receptors (TCR); CD8 beta(-) IEL bear either alpha/beta or gamma/delta TCR and are considered to be a thymus-indep endent (TI) population, probably arising locally from a small fraction of CD3(-) IEL containing the recombinant activating gene RAG proteins . Here we report that TI CD8 beta(-) IEL, whether bearing alpha/beta o r gamma/delta TCR, contain, in normal mice, mRNAs for both zeta and Fc epsilon RI gamma chains. These chains are present in their CD3-TCR co mplexes as homo- or heterodimers. In contrast, only zeta chain mRNA an d homodimers are found in gut CD8 alpha/beta(+) IEL and in peripheral T lymphocytes. Intestinal CD3(-) precursor cells contain only gamma ch ain, and CD3(-) IL-2R(+) thymocyte precursors only zeta chain mRNAs. O nly very primitive thymocyte precursors contain detectable gamma chain mRNA, and it thus appears that Fc epsilon RI gamma chain use is switc hed off at a very early stage during thymocyte differentiation. Thus, T cell differentiation in the gut epithelium differs from that occurri ng in the thymus, from which CD8 beta(+) IEL appear to derive. Use of different TCR transducing modules and CD8 accessory molecules between the TI and the thymus-derived T cell populations provides an explanati on for their difference in reactivity to antigenic stimulations and th us in selection of repertoires.