Mechanisms of lymphocyte-mediated cytotoxicity. I. The effects of anti-human lymphotoxin antisera on the cytolysis of allogeneic B cell lines by MLC-sensitized human lymphocytes in vitro.
Goat and rabbit anti-human lymphotoxin sera, IgG and F(ab')2 reagents were investigated for their capacity to effect a specific alloimmune lymphocyte-mediated cytotoxic reaction. The cytotoxic reaction employed human peripheral blood or adenoid lymphocytes sensitized in MLC to allogeneic B lymphocyte cell lines and lysis was measured in a short-term 51Cr-release assay. A polyspecific anti-LT sera (anti-WS), made against unfractionated whole supernatants from lectin-activated lymphocytes and its IgG and F(ab')2 fragments, was found to be a potent inhibitor of this reaction when the anti-WS reagent was present throughout the assay period. Absorption studies indicated the anti-WS was inhibiting cytolysis at the level of effector cell or its products. Two broadly defined antibody specificities were involved in the cytolytic-inhibitory activity of the polyspecific anti-LT; i) antigens present on the normal lymphocyte cell surface; and ii) lymphocyte surface antigens associated with activated cells. These results correlate with the previously defined antigenic structure of the LT Cx and alpha H classes. Anti-LT sera reactive with the smaller m.w. alpha and beta classes and subclasses were not inhibitory, although the anti-beta sera showed a moderate enhancing activity. The results indicated that several anti-LT antibody specificities may be required to inhibit alloimmune cytolysis. The results suggest LT molecules may mediate lymphocyte-induced alloimmune cytolysis as a multi-component toxin system, rather than as an individual toxin.
D000042:Absorption; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006041:Goats; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000276:immunology*; D011817:Rabbits
D001798:Blood Proteins; D007106:Immune Sera; D008233:Lymphotoxin-alpha