We investigated roles of α- and β-lymphotoxins in antibody dependent cell-mediated cytotoxicity(ADCC) utilizing a homologous human system; skin fibroblasts with known HLA type, allo-antiserum and blood lymphocytes. Under assay conditions using optimal amounts of priming anti-HLA antibody, maximal killing of 60-80% was achieved within 6 hours. At this time, only β-LT was present in supernatants of lytic culture; α-LT was not detected. The amounts of β-LT, as well as the kinetics of appearance, paralleled the extent and kinetics of ADCC killing by lymphocytes. Allo-antibody directed to HLA determinants not on the target cells elicited neither lysis nor β-LT release. Antisera were prepared to β-LT-containing supernatants or to partially purified α-LT. Anti-β-LT serum inhibited essentially only β-LT. Anti-α-LT inhibited from 13-38% of the total activity of standard β-LT preparations. We interpret this as either indicating a 13% contamination of the anti-α-LT with anti-β-LT activity or a 13% contamination of the standard β-LT preparation with α-LT. Both immune sera inhibited EA-rosette formation. In addition, anti-α-LT serum inhibited E-rosette formation. Anti-β-LT serum was markedly effective in inhibiting ADCC. Inhibition by anti-α-LT correlated with its anti-β-LT titer rather than with its anti-α-LT titer. Adsorptions to spleen cells essentially did not reduce the ability to block ADCC and totally removed EA-rosette inhibiting activity. These data suggest that β-LT plays a important role in ADCC target destruction.

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In order to clarify the regulatory mechanisms on human immune system, the functions of T-cells suppressing each of immunoglobulin production, mixed lymphocyte culture reaction (MLR) and generation of MLR killer were studied in vitro.
The soluble factor released from TG-cells interacted with immune complexes suppressed immunoglobulin production but not MLR nor MLR killer. In contrast, the factor in the culture supernatant of later stage of MLR suppressed MLR or generation of MLR killer but not immunoglobulin production. The cultured T-cells showed suppressive effect on both immunoglobulin production and MLR or MLR killer.
These observations indicated that suppressor mechanisms distinct from each other are operating in different immune reactions in human immune system.

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[in Japanese]

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