Mechanisms of lymphocyte-mediated cytotoxicity. III. Characterization of the mechanism of inhibition of the human alloimmune lymphocyte-mediated cytotoxic reaction by polyspecific anti-lymphotoxin sera in vitro
Ware, C.F.; Granger, G.A.
Journal of Immunology 126(5): 1934-1940
1981
ISSN/ISBN: 0022-1767 PMID: 6971314 Document Number: 181542
The mechanism of inhibition of 1 human cytotoxic T lymphocyte-mediated (CTL) reaction in vitro by a polyspecific antiserum directed against soluble products of activated lymphocytes was investigated. This antiserum was made against serum-free culture supernatants from [concanavalin A] lectin-activated human lymphocytes (anti-WS). The anti-WS shows strong neutralizing activities for both soluble and membrane forms of human lymphotoxins. The anti-WS was investigated for its site(s) of inhibition of the alloimmune CTL reaction relative to the Ca-dependent phase. The anti-WS neutralized the CTL reaction subsequent to the Ca-dependent phase, suggesting the anti-WS neutralized a lytic effector mechanism. A fluid-phase immunoadsorption assay was developed to analyze the biochemical characteristics of the antigenic determinant(s) recognized by the anti-WS. Unfractionated supernatants or defined MW regions corresponding to the MW classes of the human LT system were used to adsorb the anti-WS. Apparently unfractionated supernatants and LT-Cx fractions (> 200,000 MW) significantly reduced the capacity of the anti-WS to inhibit the alloimmune CTL reaction. .alpha.-LT fractions (70-90,000 MW) partially adsorbed the cytolytic inhibitory antibodies of the anti-WS; .beta. and .gamma. LT fractions (40-50,000 and < 20,000 MW, respectively) were ineffective. The concept that the mechanism of inhibition mediated by the anti-WS was by its capacity to interact with multiple antigenic species of LT molecules is supported. Apparently lymphotoxins are involved as a multicomponent system of cytotoxins in the lytic effector mechanism of human alloimmune cytotoxic T lymphocytes. The LT-Cx appears to represent the most likely molecular candidate for the lytic effector mechanism. A model is presented that attempts to integrate the biochemical properties of the LT system with the cellular mechanism(s) of the alloimmune cytotoxic reaction scheme.