Characterization of T cells expressing the γ/δ antigen receptor in human renal allografts

Two investigate the role of γ/δ⁺ T cells in allograft rejection, we have studied the TCR phenotype and function of lymphocytes infiltrating rejecting, rejected, and nonrejecting human renal allografts. Two-color immunohistologic staining showed that 19% of rejecting biopsies and 40% of rejected nephrectomies had significant infiltration (>10% of the total T-cell population) with γ/ggd⁺ T cells. No biopsies from nonrejecting kidneys showed >10% γ/δ⁺ T cells. Flow-cytometry analysis of T-cell populations expanded from rejecting and rejected allografts demonstrated that 33% of biopsy- and 40% of nephrectomy-derived populations had significant percentages (>10%) of γ/δ⁺ T cells. Six cell lines with increased numbers of γ/δ⁺ T cells were tested for cytolytic activity against the NK target cell line K562 and compared with cytotoxic activity of exclusively α/β T-cell populations. Lysis was noted by all γ/δ⁺, but no γ/δ^-, populations. To confirm that the cytotoxicity of these γ/δ⁺ T-cell populations was not MHC directed, one nephrectomy-derived population with 69% γ/δ⁺ T cells by cytometry and >50% by immunohistology was studied extensively. High levels of killing were seen against the NK targets K562 and Daudi as well as other malignant, benign, and third-party renal cell lines, but relevant alloantigen-expressing targets were not killed. Sterile cell sorting was used to isolate the γ/δ⁺ T cells. The γ/δ⁺ cells displayed enhanced killing of K562 while the γ/δ^- cells showed no cytolytic activity. Cytotoxicity mediated by γ/δ⁺ T cells was also demonstrated against donor-derived, untransformed renal cells. Incubation of the γ/δ⁺ cells with TCRδ1, OKT3, or anti-HLA-DR 30 minutes prior to the addition of the primary renal target or K562 failed to block the cytotoxity. These findings indicate that γ/δ⁺ T cells are frequently present in acutely rejecting human renal allografts and in some cases represent the predominant T-cell population; these cells have direct cytolytic activity against renal epithelium, and the mechanism used by these cells for killing allogeneic renal cells is NK-like. The functional characteristics of these cells are consistent with those expected of cells participating in graft destruction. Human Immunology 36, 11-19 (1993).