Skip to main content
Open Access Publications from the University of California

UC Irvine

UC Irvine Previously Published Works bannerUC Irvine

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.


The mechanism of inhibition of one 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 lectin-inactivated 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 calcium-dependent phase. The anti-WS was found to neutralize the CTL reaction subsequent to the calcium-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 m.w. regions corresponding to the m.w. classes of the human LT system were used to adsorb the anti-WS. The data indicated that unfractionated supernatants and LT-Cx fractions (>200,000 m.w.) significantly reduced the capacity of the anti-WS to inhibit the alloimmune CTL reaction. α-LT fractions (70 to 90,000 m.w.) partially adsorbed the cytolytic inhibitory antibodies of the anti-WS, whereas β and γ LT fractions (40 to 50,000 and <20,000 m.w., respectively) were ineffective. These results support 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, and thus implies that 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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View