Depressed T cell proliferative responses in Hodgkin's disease: role of monocyte-mediated suppression via prostaglandins and hydrogen peroxide.

We studied the contribution and mechanisms of monocyte-mediated suppression in the depressed T cell proliferative responses observed in patients with Hodgkin's disease. Mononuclear leukocytes from 22 untreated patients had significantly lower proliferation after stimulation with suboptimal doses of phytohemagglutinin than normals controls (p less than 0.001). When indomethacin was added to the cultures, the mean percent increase in patient proliferation exceeded that of normals (160 +/- 19% vs 81 +/- 9%; p less than 0.008), yet patient proliferation remained only 36% of normal. Catalase alone caused a minimal increase in proliferation in all cultures. When catalase plus indomethacin were added to either normal or patient cultures, however, a synergistic increase was observed. The mean percent increase in patient proliferation was 300 +/- 80%, although once again the absolute proliferative response of the patients remained subnormal (p less than 0.003). Removal of adherent monocytes from patient cultures produced increases in proliferation comparable to that observed with the addition of indomethacin. Long-term disease-free survivors of Hodgkin's disease had depressed T cell proliferation but no significant increase after the addition of indomethacin. We conclude: 1) although untreated patients with Hodgkin's disease have increased monocyte suppressor activity that is mediated by increased prostaglandin production, this is not the major cause of the depressed T cell proliferative responses observed in Hodgkin's disease; 2) depressed proliferative responses in cured Hodgkin's disease are not mediated by prostaglandins; 3) hydrogen peroxide suppresses T cell proliferation in both normals and untreated patients; and 4) other factors, probably inherent in the T cell itself, are the major cause of depressed T cell responses in Hodgkin's disease.