REGIONAL PHENOTYPIC SPECIALIZATION OF INTRAEPITHELIAL LYMPHOCYTES IN THE RAT INTESTINE DOES NOT DEPEND ON MICROBIAL COLONIZATION

Recent studies in mice and humans have provided evidence for regional specialization of gut intraepithelial lymphocytes (IEL), Here the auth ors report striking regional variability in the composition of IEL in rat small and large intestine. Two-colour immunofluorescence in situ a nalysis showed that the distribution of the CD3+ and CD3(-)IEL subpopu lations varied, the proportion of T cells (CD3+) being higher in the i leum than in the jejunum and smallest in the colon. These differences were explained by variable numbers of the T-cell receptor (TCR)alpha/b eta(+) (both CD8(+) and CD4(+)) but not the TCR gamma/delta(+) subset. Moreover, the various IEL subpopulations showed distinct intraepithel ial distribution patterns with CD4+ and CD8 alpha beta(+) T cells situ ated near the lamina propria, while CD3(-)IEL were located preferentia lly towards the adluminal part of the epithelium. Regional phenotypic variation did not depend on intestinal colonization because analogous results were obtained in germ-free rats. Conventionalization neverthel ess caused a marked relative increase of small intestinal TCR alpha/be ta(+) but not TCR gamma/delta+ IEL. This increase was more sustained i n the jejunum than ileum and eventually reduced the phenotypic IEL dif ferences between the two sites. By contrast, microbial colonization of the colon induced only a transient increase of intraepithelial TCR al pha/beta(+) cells with no permanent phenotypic alterations. Both CD3() and CD3(-)IEL contained subpopulations that expressed NKR-P1 indepen dent of intestinal colonization. These results demonstrate phenotypic specialization of IEL at different levels of the gut and suggest that the indigenous flora is not essential to this end.