Histocompatibility and natural cell-mediated cytotoxicity.
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Antibody-Dependent Cell Cytotoxicity↗
Biomedical subjects
D Akira
Publications and source records attributed to D Akira.
Role of antibodies in the specificity of natural cell-mediated cytotoxicity.
Freshly isolated effector cells expressing natural cell-mediated cytotoxicity (NCMC) against cultured target cells possessed antibodies attached to Fc receptors on their cell surfaces. A wide variety of natural antibodies in the circulation combined with the receptors on effector cells to allow recognition of the many specificities on cultured target cells and resulted in reactions with an overall appearance of nonselectiveness. The role of antibodies in the specificity of NCMC was demonstrated by recovery of NCMC by trypsinized effector cells when incubated in serum. With absorbed serum, activity was selectively weaker against the absorbing target cell. When effector cells were reconstituted with antibodies eluted from the absorbing cells, selective cytotoxicity for that cell was detected. The specificity of effector cells reconstituted with eluted antibodies confirmed the results from previous studies on specificity by direct cytotoxicity and by competitive inhibition of cytotoxicity and supported the role of antibodies in NCMC.
Antibodies, Neoplasm↗
Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum.
When effector cells from most individuals are tested directly against a number of target cells for cell-mediated cytotoxicity, most of the reactivity is non-selective. This apparent non-selectiveness is a result of specific activity against multiple antigens on target cells by each effector suspension. The specific reactions can be demonstrated through competitive inhibition of natural cell-mediated cytotoxicity. The specific inhibition of cytotoxicity by competitor cells directed our attention toward the determination of specificity to the effector cell surface. Natural cell-mediated cytotoxicity was decreased when effector cells were treated with proteolytic enzymes or low pH and regained when these cells were incubated in serum, suggesting an antibody on cell surfaces of the effector cell. Reconstitution of trypsinized effector cells with absorbed serum resulted in selective loss of cytotoxicity against the absorbing cell. To determine the role of the effector cell and the role of antibodies in natural cell-mediated cytotoxicity, effector cells from two different persons were reconstituted in the same absorbed sera. The selective pattern achieved was similar. When effector cells from the same individual were reconstituted with two different sera absorbed in the same way, the selective pattern achieved showed greater differences. We concluded that natural antibodies loosely attached to effector cells provided the specificity of natural cell-mediated cytotoxicity.
Antibodies↗
Specificities in human cell-mediated cytotoxicity.
Specificity of natural cell-mediated cytotoxicity was investigated through selective reactions detected by direct cell-mediated cytotoxicity and by inhibition of cytotoxicity through competition. Assuming that target cells reacting alike in direct cytotoxicity shared common antigens, we classified 10 target cells into three groups by target antigens: TA (target antigen) 1, 2, and 3. Partial confirmation of the three groups was achieved in the cross-competition assay. The distinction of TA 1 as a group was clear but some cross-reactivity existed between TA 2 and TA 3 cells.
Antigens, Neoplasm↗
Granulocytes as effectors in cell-mediated cytotoxicity of adherent target cells.
In the microassay for cell-mediated immunity, detachment of adherent target cells from the wells occurs to an even greater extent when tested with granulocytes than when tested with lymphocytes. Intact cells are not necessary since the sonic extract from granulocytes causes the same effect. The reaction by granulocytes appears to be mediated by enzymes, and is inhibited by the presence in the wells of hyaluronic acid. Moreover, it is limited to the detachment of adherent target cells, since neither intact nor sonically disrupted granulocytes exhibit cytotoxic activity in the chromium release assay. The detachment of target cells is also inhibited by heparin which may be used to specifically mullify the effect of granulocytes contaminating lymphocyte suspensions.
Cell Adhesion↗