The TCR δ Repertoire in Normal Human Skin is Restricted and Distinct from the TCR δ Repertoire in the Peripheral Blood

The skin and the intestinal mucosa form surfaces to external environments and share similarities in anatomic structure and immunologic defense. In healthy humans, intestinal γ/δ T cells express a highly restricted γ/δ T cell receptor repertoire whereas γ/δ T cells of the skin were thought to express a polyclonal repertoire. Herein we report, using complementarity-determining region 3 size spectratyping and nucleotide sequencing of T cell receptor DV1 and DV2 rearrangements, that the human skin is also composed of clonally expanded γ/δ T cells that are widely distributed. Identical complementarity-determining region 3 profiles and T cell receptor δ rearrangements were found in two separate skin samples that were obtained as far as 2–10 cm apart. Furthermore, analysis of peripheral blood mononuclear cells of these subjects clearly demonstrated that the skin harbors a unique population of γ/δ T cells that is distinct from that in the peripheral blood. In addition comparable data were obtained irrespective of whether DNA or RNA was analyzed, indicating that the observed oligoclonality is not secondary to the expression of large amounts of mRNA from a few activated cells. Thus, γ/δ T cells of the skin and the intestine both express an oligoclonal repertoire that enables them to respond to a variety of deleterious antigens without the need for diverse T cell receptors, possibly by recognition of stress-induced self-antigens or of conserved foreign antigens.