Impairment in proliferation, lymphokine production and frequency distribution of mitogen-responsive and interleukin-2-producing cells in Hodgkin's disease

Abstract

In this paper, we have correlated the ability of peripheral blood lymphocytes (PBL) from Hodgkin's Disease patients to proliferate in response to a mitogen, phytohaemagglutinin (PHA), with production of lymphokines interleukin-2 (IL-2) and interferon γ(IFNγ), accumulating in the activated lymphocyte culture supernatants. We have also studied the frequency distribution of PHA-responsive and IL-2-producing T cells from PBL using limiting-dilution analysis. We observed that the levels of IL-2 and IFNγ in the supernatants of activated lymphocytes from patients with Hodgkin's disease were significantly reduced compared to those of healthy donors. Substage-B patients showed marked reduction in the ability to produce IFNγ. Levels of IL-2 and IFNγ in the culture supernatants of PBL from Hodgkin's disease patients correlated positively with proliferative responses, when analysed by linear regressison (r=0.79 andr=0.60 respectively). However, production of the two lymphokines by activated lymphocytes from the same patients did not correlate (r=+0.04). Further, the frequencies of PHA-responsive cells and IL-2-producing cells in the PBL of patients with Hodgkin's disease (ranges 1/111-1/554 and 1/3009-1/6709 respectively) were also less than those of the healthy donors (ranges 1/80-1/181 and 1/761-1/1828 respectively). Proliferation, IL-2 production in bulk cultures and frequencies of PHA-responsive and IL-2-producing cells correlated well in individual healthy donors. Whereas, one patient (BC 11 214) with a frequency of PHA-responsive cells within normal limits had a very low frequency of IL-2-producing cells. Taken together, the results indicate abnormalities in cytokine production and frequency distribution of cells required for amplification of immune response in patients with Hodgkin's disease.