Evidence for clonal selection of γ/δ T cells in response to a human pathogen

Abstract

T cells bearing γ/δ antigen receptors comprise a resident population of intraepithelial lymphocytes in organs such as skin, gut, and lungs, where they are strategically located to contribute to the initial defense against infection. An important unsolved question about antigen-driven γ/δ T cell responses regards the breadth of their T cell receptor (TCR) repertoire, since many specific epithelial compartments in mice display limited diversity. We have examined the diversity of TCR δ gene expression among human γ/δ T cells from skin lesions induced by intradermal challenge with Mycobacterium leprae. We show that the vast majority of γ/δ cells from M. leprae lesions use either Vδ1-Jδ1 or Vδ2-Jδ1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity. This contrasts markedly with the extensive diversity of γ/δ T cells from peripheral blood of these same individuals, as well as skin from normal donors. These results indicate that the γ/δ response to M. leprae involves the selection of a limited number of clones from among a diverse repertoire, probably in response to specific mycobacterial and/or host antigens.