Evidence of 'K'-Cell Killing by Alloactivated, Fc-Receptor-Bearing Cytotoxic T Lymphocytes

Upon in vivo alloactivation of Ig-anti-Ig column-purified splenic 'T' cells in lethally irradiated allogeneic recipients, a variable proportion of donor-derived cytotoxic T lymphocytes (CTLs) are able to bind IgG antibody-coated erythrocytes through surface Fc receptors (FcR) and form rosettes. The use of fractionation procedures based on the ability of these cells to form rosettes has enabled us to separate FcR-positive CTLs from FcR-negative CTLs and to examine the ability of these two cell populations to perform as effector cells in direct T-cell-mediated killing and in antibody-dependent cellular cytotoxicity. A series of experiments, either by direct isolation of the two cell populations or by deletion of the FcR-positive population by filtration through complexed immunoglobulin columns (Ig-anti-Ig), has shown both populations to be efficient in direct T-cell mediated cytotoxicity against the relevant target cell. The striking difference between the two populations is the exclusive ability of the FcR-positive population to function as effector cells in antibody-dependent cellular cytotoxicity (ADCC). Purification steps before in vivo alloactivation of our responding cells for the removal of 'B' cells and FcR-bearing cells with 'K'-cell activity, followed by procedures to remove phagocytic and adherent cells in the resulting immune spleen cell preparation and, finally, b y velocity sedimentation of the rosetting and nonrosetting blasts from the small lymphocyte population, has resulted in a population of FcR-positive cells 98% positive for the Thy 1.2 alloantigen. These fractionation steps and immunofluorescence criteria of purity strongly favor the contention that the ADCC activity within the FcR-positive T-cell population is indeed a property of the CTL itself.