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 CD8αα⁺ 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 CD8αα⁺ 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 CD8αβ⁺ 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.