Failure of Certain Cytotoxic Lymphocytes to respond mitotically to Phytohaemagglutinin

Abstract

CYTOTOXIC activity by lymphocytes has attracted considerable interest because of its possible role in the rejection of grafted tissues and neoplastic cells. Damage to target cell caused by lymphoid cells was first demonstrated in 1960 by Govaerts¹, and there were several subsequent reports of immunologically specific cytotoxicity towards target cells by lymphoid cells from sensitized donors. These have recently been reviewed extensively². The situation was complicated when cytotoxic activity by lymphocytes from apparently unsensitized donors was demonstrated in 1964 by Holm et al.³, in cultures of lymphoid cells and target cells when phytohaemagglutmin (PHA) was incorporated into the medium. Holm and Perlmann⁵ later showed that several other circumstances could lead to immunologically non-specific cytotoxic activity by lymphocytes. The induction of cytotoxicity in all these systems seemed to correlate well with increased mitogenic activity in the lymphocyte population tested. Recently it has been shown that immunologically nonspecific cytotoxic activity can be evoked from lymphocytes when the target cell antigens are complexed with certain antibody^5–7. This effect has been demonstrated in a wide variety of species including man⁸, and does not seem to require the participation of complement components. We have previously reported that much of the immunologically specific target cell damage by lymphocytes in rats is dependent on immunoglobulin sensitization of target cells⁹. The sensitizing antibody, in this case, is synthesized by lymphocytes which are not themselves cytotoxic. Bubeník, Perlmann and Hašek¹⁰ have provided evidence that this mechanism brings about homograft rejection in donors made tolerant to graft antigens. Although there has been no report of antibody-induced cytotoxicity being associated with blast transformation, transformation in response to antigen-antibody complexes has been described^11,12.