Role of gamma delta T cells in tumor immunity and their control by NK receptors

Soon after the discovery of the T-cell receptor (TCR) of gamma delta type on human T-lymphocytes, most gamma delta T-cell clones were described as displaying strong cytotoxic activity against diverse tumor cell lines. Initially, this cytotoxic activity by interleukin-2 (IL-2)-activated gamma delta T lymphocytes was referred to as 'lymphokine-activated killer' activity, comparable to lysis by activated natural killer (NK) cells. However, it had been speculated that gamma delta T cells 'might be more specific' for distinct tumor cells than NK cells. Nevertheless, there is still controversy as to whether the gamma delta TCR is directly involved in the recognition of some tumor cells by most gamma delta T lymphocytes. In part, this is due to the fact that the target molecules for most gamma delta T cells on tumor cells remain undefined. On the other hand, the direct involvement of the TCR in target cell recognition is difficult to demonstrate in functional assays.