Distinct tumour specificity and IL-7 requirements of CD56(-) and CD56(+) subsets of human gamma delta T cells

gamma delta T cells are believed to recognize tissue injury caused by infec tions, tumours, as well as chemical and physical agents. The present study was carried out to study the feasibility of the ex vivo expansion of gamma delta T cells from healthy individuals, and to determine their functional c apacity against tumours. We selectively expanded the peripheral gamma delta T cells of five donors against a myeloma cell line, XG-7. Under optimal co nditions, the resulting bulk cultures comprised about 82% of the gamma delt a T cells, more than 90% of which showed the T-cell receptor (TCR)-V gamma9 delta2 rearrangement. These gamma delta T-cell cultures exhibited TCR-gamm a delta dependent cytotoxicity against different tumour cell lines includin g Molt-4, BJAB, Epstein-Barr virus (EBV) transformed lymphoid cell lines (L CL), and the nasopharyngeal carcinoma (NPC) cell lines, CNE2 and 915, in ad dition to the stimulator XG-7. By competitive cytotoxicity assays, the gamm a delta T cells demonstrated recognition of at least three distinct target specificities expressed by Molt-4, CNE2 and LCL, respectively, which were r elated to that expressed by the stimulator XG-7 cells. The recognition of t he specificity expressed by XG-7 and Molt-4 was further shown to require th e participation of heat shock protein (HSP). The specificity expressed by C NE2 and 915 was preferentially recognized by the CD56(-) subset of gamma de lta T cells, which could be sustained in the presence of interleukin (IL)-7 . These results suggested that gamma delta T-cell immunity against tumour c ell lines may be acquired in response to other types of tissue injury and, hence, implicates a role for their use in the prevention and treatment of t umours.