Human intestinal V delta 1+ T cells obtained from patients with colon cancer respond exclusively to SEB but not to SEA.
The function and activation requirements for gamma delta T cells residing in the human intestine are still poorly defined. We have established two gamma delta + T cell tumor-infiltrating lymphocyte (TIL) lines derived from a primary colorectal cancer (gamma delta TIL No. 3481), and from a colorectal cancer lesion metastatic to the liver (gamma delta TIL No. 7279). Both gamma delta TIL lines used exclusively the V delta 1 segment and predominantly the V gamma 2 segments of the T cell receptor (TCR) variable regions and lysed allogeneic colorectal cancer cell lines, e.g. HCT 116, but not natural killer/lymphokine-activated-killer-sensitive target cell lines, e.g. K562 or Daudi. gamma delta 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)-gamma release. Both gamma delta 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 gamma delta + T cell line responded to SEA as measured by IFN-gamma release of T cell proliferation. In marked contrast, SEB induced T cell proliferation and IFN-gamma release in the absence of stimulator cells. SEB induced secretion of IFN-gamma by gamma delta T cells which could be augmented if stimulator cells (HCT116) were also added to gamma delta T cells. On the basis of these data, we suggest that intestine-derived V delta 1/V gamma 2+ T cells respond preferentially to SEB and not to SEA. This disparity may reflect the inherently higher affinity of individual gamma delta TCR subsets for SEB but not to SEA and/or indicate that a subset of gamma delta + TILs in patients with colon cancer may be preferentially expanded with a TCR rearrangement favoring the interaction with SEB. The induction of IFN-gamma release and proliferative gamma delta + T cell responses by SEB suggests a pivotal role for intestinal gamma delta T cells in mediating immune responses against bacteria and bacterial products, or potentially in anti-tumor-directed immunity. Such immune responses mediated by gamma delta + T cells may take place prior to the maturation of antigen-specific MHC-restricted alpha beta + T cell responses.
Maeurer
M
M
Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pa., USA.
Zitvogel
L
L
Elder
E
E
Storkus
W J
WJ
Lotze
M T
MT
D000942:Antigens, Bacterial / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology*; D015179:Colorectal Neoplasms; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008113:Liver Neoplasms / Q000556:secondary; D008213:Lymphocyte Activation / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013210:Staphylococcus / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000942:Antigens, Bacterial; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018089:Superantigens; D007371:Interferon-gamma