An analysis of the relationship between gamma delta T cell receptor V gene usage and non-major histocompatibility...

gamma delta T cells are capable of mediating non-major histocompatibility complex (MHC) restricted lysis of a variety of tumour cell lines. The mechanism of this lysis and its significance in tumour immunity are not clear. We have used a panel of five malignant mesothelioma (MM) cell lines, as well as standard tumour targets K562 and Daudi, to investigate some of the factors which could be involved in non-MHC restricted cytotoxicity mediated by gamma delta T cells. Individual MM cell lines, representing a panel of lines derived from a single cell type, varied in their susceptibility to lysis by gamma delta T cell clones. Individual gamma delta T cell clones also showed unique cytotoxic profiles, and differed in their cytotoxic potential. T cell receptor (TCR) V gamma gene usage correlated with the ability of clones to lyse Daudi or K562; clones lysing Daudi expressing V gamma 9 and clones lysing K562 expressing V gamma I subgroup genes. No strict correlation between V gamma and V delta gene usage and MM reactivity was, however, demonstrable. There was also no correlation between gamma delta T cell lysis of MM cell lines and the capacity of gamma delta T cells to produce interferon-gamma, tumour necrosis factor-alpha, interleukin-2 or interleukin-4, nor with their expression of CD8.