Studies of lymphocytotoxins in infectious mononucleosis and systemic lupus erythematosus: evidence for immune complex-mediated cytotoxicity.

The hypothesis that serum lymphocytotoxins are antigen-antibody complexes was examined. High molecular weight fractions from the sera of eighteen patients with infectious mononucleosis (IM), thirteen patients with systemic lupus erythematosus (SLE) and six healthy controls, were prepared by precipitation with polyethylene glycol 6000 (PEG). The lymphocytotoxic activity (LCA) of these PEG precipitates was significantly greater (P less than 0.01) than that of the corresponding sera and a significant correlation (r = 0.66, P less than 0.01) was observed between the LCA of sera and the PEG precipitates. In contrast to the concentration of LCA in the PEG precipitates, the heterophil antibody titres of the precipitates from IM sera were significantly less (P less than 0 05) than serum titres. Antisera raised against PEG precipitates from sera from nine patients with IM contained significant LCA. The nature of this LCA differed from that of the LCA in the original sera in temperature dependence and the molecular size. Antigen-antibody complexes in seven sera (four IM, three SLE) were dissociated at low pH (3.0) and fractionated by gel filtration at pH 3.9. The LCA of these fractions was compared with the LCA of equivalent fractions obtained by gel filtration at pH 7.2. The heterophil antibody present in sera from patients with IM and the cytotoxicity of anti-lymphocyte globulin (ALG) were used as 'antibody controls'. In this way it was shown that the LCA in patient sera, but not heterophil antibody or ALG cytotoxicity was significantly reduced (P less than 0.001) by low pH gel filtration.