Human intestinal V delta 1(+) T lymphocytes recognize tumor cells of epithelial origin

gamma delta T cells can be grouped into discrete subsets based upon their expression of T cell receptor (TCR) variable (V) region families, their tissue distribution, and their specificity. V delta 2(+) T cells constitute the majority of gamma delta T cells in peripheral blood whereas V delta 1(+) T cells reside preferentially in skin epithelium and in the intestine. gamma delta T cells are envisioned as first line host defense mechanisms capable of providing a source of immune effector T cells and immunomodulating cytokines such as interleukin (IL) 4 or interferon (IFN) gamma. We describe here the fine specificity of three distinct gamma delta tumor-infiltrating lymphocytes (TIL) obtained from patients with primary or metastatic colorectal cancer, that could be readily expanded in vitro in the presence of IL-1 beta and IL-7. Irrespective of donor, these individual gamma delta T cells exhibited a similar pattern of reactivity defined by recognition of autologous and allogeneic colorectal cancer cells, renal cell cancer, pancreatic cancer, and a freshly isolated explant from human intestine as measured by cytolytic T cell responses and by IFN-gamma release. In contrast, tumors of alternate histologies were not lysed, including lung cancer, squamous cell cancer, as well as the natural/lymphocyte-activated killer cell-sensitive hematopoietic cell lines T2, C1R, or Daudi. The cell line K562 was only poorly lysed when compared with colorectal cancer targets. Target cell reactivity mediated by V delta 1(+) T cells was partially blocked with Abs directed against the TCR, the beta 2 or beta 7 integrin chains, or fibronectin receptor. Marker analysis using flow cytometry revealed that all three gamma delta T cell lines exhibit a similar phenotype. Analysis of the gamma delta TCR junctional suggested exclusive usage of the V delta 1/D delta 3/J delta 1 TCR segments with extensive (less than or equal to 29 bp) N/P region diversity. T cell recognition of target cells did not appear to be major histocompatibility complex restricted or to be cell-elated with target cell expression of heat-shock proteins. Based on the ability of some epithelial tumors, including colorectal, pancreatic, and renal cell cancers to effectively cold target inhibit the lysis of colorectal cancer cell Lines by these V delta 1(+) T cell lines, we suggest that intestinal V delta 1(+) T cells are capable of recognizing cell surface Ag(s) shared by tumors of epithelial origin.