Human intestinal V(δ)1+ T cells obtained from patients with colon cancer respond exclusively to SEB but not to SEA

The function and activation requirements for γδ T cells residing in the human intestine are still poorly defined. We have established two γδ+ T cell tumor-infiltrating lymphocyte (TIL) lines derived from a primary colorectal cancer (γδ TIL No. 3481), and from a colorectal cancer lesion metastatic to the liver (γδ TIL No. 7279). Both γδ TIL lines used exclusively the V(δ)1 segment and predominantly the V(γ)2 segments of the T cell receptor (TCR) variable regions and lysed allogeneic colorectal cancer cell lines, e.g. HCT116, but not natural killer/lymphokine-activated-killer-sensitive target cell lines, e.g. K562 or Daudi. γδ T cell effector functions were evaluated on the basis of their recognition and cytolysis of colorectal cancer cell lines, T cell proliferation, and interferon (IFN)-γ release. Both γδ T cell lines exhibited similar responses to the staphylococcal superantigens (SE) A and B. SEA and SEB did not influence target cell cytolysis of colon cancer targets. Neither γδ+ T cell line responded to SEA as measured by IFN-γ release of T cell proliferation. In marked contrast, SEB induced T cell proliferation and IFN-γ release in the absence of stimulator cells. SEB induced secretion of IFN-γ by γδ T cells which could be augmented if stimulator cells (HCT 116) were also added to γδ T cells. On the basis of these data, we suggest that intestine-derived V(δ)/V(γ)2+ T cells respond preferentially to SEB and not to SEA. This disparity may reflect the inherently higher affinity of individual γδ TCR subsets for SEB but not to SEA and/or indicate that a subset of γδ+ TILs in patients with colon cancer may be preferentially expanded with a TCR rearrangement favoring the interaction with SEB. The induction of IFN-γ release and proliferative γδ+ T cell responses by SEB suggests a pivotal role for intestinal γδ T cells in mediating immune responses against bacteria and bacterial products, or potentially in anti-tumor-directed immunity. Such immune responses mediated by γδ+ T cells may take place prior to the maturation of antigen-specific MHC-restricted αβ+ T cell responses.