Proliferative and cytolytic responses of human gamma delta T cells display a distinct specificity pattern

The function and physiological role of gamma delta T cells are still unknown. Concerning the specificity of these cells, a proliferative response towards microbial ligands has been noted, whereas in terms of effector functions in humans a cytolytic activity against a variety of tumour targets is most prominent. Here we show data demonstrating that the cytolytic activity of activated human gamma delta T cells does not reflect the specificity of these cells in primary in vitro stimulation; moreover, we provide evidence that the recognition of target cells by gamma delta T cells can have different qualities. gamma delta T cells proliferate vigorously in primary in vitro reaction upon stimulation with various B-cell tumour lines but not with the T-cell lines Jurkat or Molt-4. However, gamma delta T cells stimulated primarily with phytohaemagglutinin or with cells from B-cell lines gain unrestricted cytolytic activity against a broad set of tumour targets, including Jurkat and Molt-4; the same set of targets is capable of inducing release of serine esterases (SE) from gamma delta T-effector cells. Whereas the cytolytic activity in the 51Cr-assay against the B-cell lines and against Molt-4 depends on the presence of Ca2+ ions in the assay, the lysis of Jurkat cells is only slightly reduced upon removal of Ca2+ from the medium; the SE release, however, is Ca2+ dependent in all cases. Taken together, these data suggest several different ways of target cell recognition by gamma delta T cells leading to either proliferation or triggering of cytolytic activity, and argue against an involvement of the gamma delta T-cell receptor in the cytotoxic activity of gamma delta T cells.