MULTIPLE DEFECTS OF T-HELPER CELL-FUNCTION IN NEWLY-DIAGNOSED PATIENTS WITH HODGKINS-DISEASE

T helper cell(TH) function, as assessed by interleukin-2 (IL-2) produc tion and [H-3]thymidine incorporation, was studied in 47 newly diagnos ed untreated patients with Hodgkin's disease (HD) and 34 healthy contr ols. Three different stimuli were used to stimulate in vitro periphera l blood mononuclear cells (PBMC): influenza A vaccine (FLU), HLA alloa ntigens (ALLO) and phytohaemagglutinin (PHA). Four different patterns of TH function were observed in HD patients: (1) IL-2 production in re sponse to all of the stimuli (40%); (2) IL-2 production in response to ALLO and PHA but not to FLU (26%); (3) IL-2 production in response to PHA alone (19%); and (4) failure to respond by IL-2 production to any of the three of the stimuli (15%). Thus, defective in vitro TH functi on was detected in the majority of these patients (60%). Defective TH function was observed in none of the 34 controls. Severely compromised TH function (patterns 3 and 4) tended to be associated with more adva nced clinical presentation and more compromised haematological paramet ers (P < 0.05). The IL-2 production assay was more sensitive than the proliferative assay as only 30% of the HD patients failed to prolifera te in response to FLU, and none failed to proliferate in response to e ither ALLO or PHA; this assay can detect subtle, multiple patterns of immune dysregulation in untreated HD patients. Our results suggest tha t HD is associated with a fundamental dysregulation in TH function, il lustrate the complexity of such dysregulation, and raise the possibili ty that HD progression will be associated with a type-1-type-2 switch in immunoregulatory cytokine production.