Different use of T cell receptor transducing modules in two populations of gut intraepithelial lymphocytes are related to distinct pathways of T cell differentiation

Abstract

Most gut intraepithelial cells (IEL) of the mouse are T cells that bear CD8 molecules, present either as α-β chain heterodimers (CD8β+) or as α chain homodimers (CD8β-). All CD8β+ IEL bear α/β T cell receptors (TCR); CD8β- IEL bear either α/β or γ/δ TCR and are considered to be a thymus-independent (TI) population, probably arising locally from a small fraction of CD3- IEL containing the recombinant activating gene RAG proteins. Here we report that TI CD8β- IEL, whether bearing α/β or γ/δ TCR, contain, in normal mice, mRNAs for both ζ and FcεRIγ chains. These chains are present in their CD3-TCR complexes as homo- or heterodimers. In contrast, only ζ chain mRNA and homodimers are found in gut CD8α/β+ IEL and in peripheral T lymphocytes. Intestinal CD3- precursor cells contain only γ chain, and CD3- IL-2R+ thymocyte precursors only ζ chain mRNAs. Only very primitive thymocyte precursors contain detectable γ chain mRNA, and it thus appears that FcεRI γ chain use is switched off at a very early stage during thymocyte differentiation. Thus, T cell differentiation in the gut epithelium differs from that occurring in the thymus, from which CD8β+ 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 explanation for their difference in reactivity to antigenic stimulations and thus in selection of repertoires.