Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut

Abstract

Two populations of CD8+ IEL generally express restricted, but apparently random and non-overlapping TCR repertoires. Previous studies in mice suggested that this could be explained by a dual origin of CD8+ IEL, i.e. that CD8αβ+ IEL derive from a few peripheral CD8+ T cell lymphoblasts stimulated by microbial antigens in gut-associated lymphoid tissue, whereas CD8α α+ IEL descend from an inefficient intestinal maturation pathway. We show here that the gut mucosa, instead, becomes seeded with surprisingly broad and generally non-overlapping CD8 IEL repertoires and that oligoclonality is induced locally after microbial colonization. In germ-free (GF) rats, both CD8αβ+ and CD8α α+ IEL displayed surprisingly diverse TCR Vβ repertoires, although β-chain diversity tended to be somewhat restricted in the CD8αα+ subset. CDR3 length displays in individual Vβ-Cβ and Vβ-Jβ combinations generally revealed polyclonal distributions over 6-11 different lengths, similar to CD8+ lymph node T cells, and CDR3β sequencing provided further documentation of repertoire diversity. By contrast, in ex-GF rats colonized with normal commensal microflora, both CD8α β+ and CD8αα+ IEL displayed oligoclonal CDR3 length distributions for most of the Vβ genes analyzed. Our data suggest that microbial colonization induces apparently random clonal expansions of CD8αβ+ and CD8αα+ IEL locally in the gut. © 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.