Generation of cytotoxic T lymphocytes to autologous human leukaemia cells by sensitisation to pooled allogeneic normal cells

Abstract

MANY murine and human tumour cells express cell surface antigens cross-reactive with histocompatibility antigens that are expressed on normal cells of unrelated individuals of the species^1–7. One approach for generating cytotoxic lymphocytes capable of lysing autologous or syngeneic tumour cells therefore might be to sensitise to the appropriate cross-reactive alloantigen(s). Results obtained in our laboratory indicate that lymphocytes sensitised in mixed leukocyte culture to a pool of normal cells from 20 unrelated individuals⁸ lyse virtually all allogeneic target cells⁹, suggesting that the ‘pool’ presents essentially all the target determinants for cytotoxic T lymphocytes (CTL) expressed on normal human cells. We therefore hypothesised that sensitisation of T cells to the ‘pool’ may be a means for generating CTL capable of lysing autologous morphologically transformed cells without the need to experimentally define which alloantigen specificities are expressed on particular transformed cells¹⁰. One model in which we have recently demonstrated the efficacy of pool sensitisation involves Epstein–Barr virus transformed human lymphoblastoid cell lines (LCL); normal T lymphocytes sensitised in vitro against the pool lyse autologous ⁵¹Cr-labelled LCL cells but not autologous normal T cells, B cells or mitogen-induced blast cells¹¹. Studies were thus undertaken to determine whether leukaemia cells, which are incapable of stimulating cytotoxic responses in autologous lymphocytes^12–14, would be lysed by T cells from patients sensitised in vitro with pooled allogeneic cells. We report here that ‘pool’ sensitisation of T cells from patients with hairy cell leukaemia (leukaemic reticuloendotheliosis) gives rise to CTL that lyse autologous leukaemia cells but not autologous normal lymphocytes.