Impaired Lymphocyte Transformation in Hodgkin's Disease. EVIDENCE FOR DEPLETION OF CIRCULATING T-LYMPHOCYTES

Abstract

The kinetics of lymphocyte transformation induced by phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were studied daily, with blood lymphocytes from normal individuals and from untreated patients in all stages of Hodgkin's disease (HD). In addition, spleen lymphocytes and lymph node lymphocytes were studied with similar techniques.Peripheral blood lymphocyte transformation stimulated by PHA was found to be depressed in all patients with HD (including those with localized disease and no symptoms) when small numbers of lymphocytes were cultured and studied during a 7-day period. Most patients with HD had an increased number of cells circulating in their blood which were actively synthesizing DNA. HD lymphocytes which demonstrated the highest initial rate of spontaneous DNA synthesis usually did not respond to PHA stimulation. Blood lymphocytes from normal individuals responded equally well to PHA and PWM in our system. HD blood lymphocytes consistently responded better to PWM than to PHA, with the response to PWM frequently within the normal range. Unless the spleen was extensively infiltrated with HD, spleen lymphocytes from patients with HD responded to PHA, even though the blood lymphocyte response was severely reduced. Lymph node lymphocyte response to PHA from patients with HD was variable, but correlated roughly with the blood lymphocyte response. It is hypothesized from the data presented that in HD, circulating thymus-dependent (T-)lymphocytes are stimulated by the presence of active disease. This stimulation of T-lymphocytes leads to a circulating T-cell depletion and to an increase in the number of cells circulating that are active in DNA synthesis. The degree of impairment of cell-mediated immunity would then depend upon the degree of T-lymphocyte depletion.