The TCR delta repertoire in normal human skin is restricted and distinct from the TCR delta repertoire in the peripheral blood

The skin and the intestinal mucosa form surfaces to external environments a nd share similarities in anatomic structure and immunologic defense. In hea lthy humans, intestinal gamma/delta T cells express a highly restricted gam ma/delta T cell receptor repertoire whereas gamma/delta T cells of the skin were thought to express a polyclonal repertoire. Herein we report, using c omplementarity-determining region 3 size spectratyping and nucleotide seque ncing of T cell receptor DV1 and DV2 rearrangements, that the human skin is also composed of clonally expanded gamma/delta T cells that are widely dis tributed, identical complementarity-determining region 3 profiles and T cel l receptor delta rearrangements were found in two separate skin samples tha t were obtained as far as 2-10 cm apart. Furthermore, analysis of periphera l blood mononuclear cells of these subjects clearly demonstrated that the s kin harbors a unique population of gamma/delta T cells that is distinct fro m that in the peripheral blood. In addition comparable data were obtained i rrespective of whether DNA or RNA was analyzed, indicating that the observe d oligoclonality is not secondary to the expression of large amounts of mRN A from a few activated cells. Thus, gamma/delta T cells of the skin and the intestine both express an oligoclonal repertoire that enables them to resp ond to a variety of deleterious antigens without the need for diverse T cel l receptors, possibly by recognition of stress-induced self-antigens or of conserved foreign antigens.