REGIONAL SPECIALIZATION OF INTRAEPITHELIAL T-CELLS IN THE MURINE SMALL AND LARGE-INTESTINE

We investigated intraepithelial T cells from the small intestine, SI (jejunum, ileum) and the large intestine, LI (colon) of euthymic (BALB/c, H-2(d); C.B-17+/+, H-2(d); C57BL/6, H-2(b)) and athymic (C57BL/6 nu/nu; BNX bg/bg nu/nu xid/xid) mice. From individual euthymic and athymic mice, 7 x 10(6) intraepithelial lymphocytes (IEL) per mouse were isolated from the SI. Ten-fold lower numbers of IEL were obtained from the LI epithelium (4 x 10(5) IEL per mouse). Thymus-dependent and -independent T cells represented > 80% of SI-IEL but the fraction of T cells was reduced from 20% to 40% in LI-IEL. In euthymic mice, alpha beta T cells predominated in SI-IEL and in particular in LI-IEL populations, while SI-IEL and LI-IEL populations of athymic mice contained predominantly gamma delta T cells. The intraepithelial T cell subset distribution was different in SI versus LI: mainly CD8(+) T cells were present in the SI, but a large CD4(+) T cell subset was present in the LI. 'Double positive' CD4(+) CD8 alpha(+) T cells were present mainly in the SI epithelium but were rare in the LI epithelium. In euthymic as well as athymic mice, T cells expressing the homodimeric CD8 alpha alpha isoform predominated in the SI epithelium, while T cells expressing the heterodimeric CD8 alpha beta isoform predominated in the LI epithelium. LI-derived TCR alpha beta(+) IEL displayed the CD2(+) CD28(+) LPAM-1/2(-) M290(+) phenotype, and a fraction of them expressed the L-selectin LECAM-1. In contrast, a large fraction of TCR alpha beta(+) SI-IEL was CD2(-) CD28(-) LPAM-1/2(-) M290(+) and LECAM-1(-). RAG-1/2 expression was detectable by RT-PCR in IEL from the SI but not the LI, Striking differences in phenotype were thus apparent between thymus-dependent and thymus-independent T cells in the epithelial layer of the jejunum/ileum and the colon of the mouse.