Interleukin 15 controls the generation of the restricted T cell receptor repertoire of gamma delta intestinal intraepithelial lymphocytes.

The gammadelta T cells are prevalent in the mucosal epithelia and are postulated to act as 'sentries' for maintaining tissue integrity. What these gammadelta T cells recognize is poorly defined, but given the restricted T cell receptor (TCR) repertoire, the idea that they are selected by self antigens of low complexity has been widely disseminated. Here we present data showing that the generation of the restricted TCR variable gamma-region gene repertoire of intestinal intraepithelial lymphocytes was regulated by interleukin 15, which induced local chromatin modifications specific for the variable gamma-region gene segment and enhanced accessibility conducive to subsequent targeted gene rearrangement. This cytokine-directed tissue-specific TCR repertoire formation probably reflects distinct TCR repertoire selection criteria for gammadelta and alphabeta T cell lineages adopted for different antigen-recognition strategies.