Studies of human sera with cytotoxic activity

Abstract

A B S T R A C T 42 human sera showing in vitro cytotoxic activity of restricted or broad HL-A specificities with test human lymphocytes were studied for the molecular and immunoglobulin class of cytotoxic antibody using sucrose gradient separations, DEAE-cellulose chromatography, and Sephadex G-200 gel filtration. Sera originated from patients with previous multiple pregnancies (19), multiply transfused patients (8), subacute bacterial endocarditis (4), systemic lupus (2), and human umbilical cord sera (9). In 32 of 42 instances, predominant cytotoxic activity was found in high molecular weight gradient fractions; however, DEAE chromatographic separations revealed cytotoxic activity in initial buffer fractions containing primarily -vG globulin. Gradient separations of cytotoxic activity within initial 'vG DEAE fractions showed localization of cytotoxicity only in high molecular weight materials.Confirmation of high molecular weight YG cytotoxic activity was obtained by resistance to mercaptoethanol treatment, abolition of activity after absorption only with specific anti-yG antisera, and by the finding that high molecular weight cytotoxic activity in gradients or gel filtration run at neutral pH 7.4 became 7S when separations were rerun at an acidic pH of 4.0. Such 7S activity again became rapidly sedimenting when the same fractions were again rerun in gradients at neutral pH.19S iM cytotoxic activity was documented in a panel of 15 human sera containing anti-"I" cold agglutinins. In this instance the cytotoxic activity appeared to be related to the cold agglutinin antibody since it was mercaptoethanol sensitive and could be demonstrated in monoclonal antibody eluates containing primarily -yM.

Lymphocytotoxic antibodies in family members of patients with systemic lupus erythematosus.

“…Lymphocytotoxic antibodies are rarely found in normal individuals (9) execpt after multiple pregnancies or transfusions (19). Moreover, the distribution of lymphocytotoxins far exceeded that of other serologic markers such as antinuclear antibodies or gamma globulin elevations recorded during previous family studies of SLE probands (20,21).…”

Antibody-Associated Lymphotoxin in Acute Infection

“…When the cytotoxicity test was done on RFC's (T cells) and n-RFC's (B cells) (11)(12)(13) (2)(3)(4)(5)(6)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Some of the previously described lymphocytotoxins showed cytolytic activity best at cold temperatures (150C) and complement dependency.…”

Antibody-dependent cell-mediated cytotoxicity in selected autoimmune diseases.

“…The inhibition of normal lymphocyte ADCC activity by 7S fractions of SLE sera was probably due to the presence of antilymphocyte antibodies of the IgG class. Such antibodies are known to exist in SLE (23) and are probably responsible for inhibition of the mixed lymphocy-te reaction. A third mechanism might involve antibodies specific for K cells which could sterically interfere with functional sites on these effector cells.…”