Human lymphocyte-eosinophil interactions. I. Modulation of phytohemagglutinin-induced lymphocyte proliferation by eosinophils

Do eosinophils modulate lymphocyte function? This question was studied by examining the effect of purified eosinophils (eos) on lectin-induced human lymphocyte proliferation. Intact resting or zymosan-stimulated eos or their extracts were cocultured with phytohemagglutininstimulated mononuclear cells in vitro and [³H]thymidine uptake was measured at 72 hr. Zymosan-stimulated eos consistently suppressed (up to 90%) the lectin-induced proliferative response by a noncytotoxic mechanism. Freeze-thaw extracts from zymosan-stimulated eos also significantly suppressed lymphocyte proliferation to a similar degree. The amount of suppression was directly proportional to the number of eos or the amount of extract added to the lymphocyte cultures. Intact resting eos and their extracts occasionally exhibited suppressive effects (up to 40%) on lymphocyte proliferation; this suppression, however, was always less than that of activated eos or their extracts. Eos pretreated with the protein synthesis inhibitor, pactamycin, exhibited significantly less suppressive activity, suggesting that a protein was responsible in part for the reduction in proliferation. The addition of Superoxide dismutase or catalase to the eos-mononuclear cell cocultures did not reduce the amount of suppression observed, thus making it unlikely that active oxygen products were involved in the mechanism of suppression. Heating extracts from stimulated eos to 80 °C for 30 min resulted in partial loss of suppressive activity while extensive dialysis of the extracts had no effect. The studies reported here provide evidence that a nondialyzable and heat sensitive factor(s) produced by stimulated eos may exert feedback inhibition of lymphocyte function.