Effect of Concanavalin A on Lymphocyte-mediated Cytotoxicity

Abstract

CELLULAR immunity is of primary importance in graft reactions. Sensitization seems to be based on surface interactions between small lymphocytes and cell-bound transplantation antigens; the effector mechanism involves contact interactions between sensitized lymphocytes and the grafted cells. Lymphocytes recognize cell membrane antigens and cause injury to the grafted cells essentially by cell surface processes, the nature of which is not clear. The application of surface-active substances, at both the sensitization and the effector phase, could be expected to make clear some aspects of cell contact interactions involved in graft reaction. We have studied, therefore, the effects of concanavalin A (conA) on a graft reaction system. ConA is a protein molecule with two sugar-binding sites^1–6, which can interact with sugar moieties on cell surfaces^7–9. The graft reaction system we used^10,11 involved the sensitization of rat lymphocytes against mouse antigens by culturing the lymphocytes on monolayers of mouse fibroblasts for 5 days. This sensitization is characterized by a morphological transformation of small lymphocytes into medium or large cells¹². The sensitized lymphocytes are capable of lysing mouse cells which are antigenically identical to the sensitizing cells. Antibodies are not produced, and the lytic reaction thus requires direct contact between the lymphocytes and the target cells¹³. The rate of lysis is measured by plating the sensitized lymphocytes on fibroblasts labelled with Na⁵¹CrO₄ and measuring the amount of radioactivity released into the culture medium^14,15.