title: 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 gamma (IFN gamma), 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 IFN gamma 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 IFN gamma. Levels of IL-2 and IFN gamma in the culture supernatants of PBL from Hodgkin's disease patients correlated positively with proliferative responses, when analysed by linear regression (r = 0.79 and r = 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.
authors.affiliation: Cancer Research Institute, Tata Memorial Centre, Parel, Bombay, India.
authors.forename: R N
authors.initials: RN
authors.lastname: Damle
authors.forename: S H
authors.initials: SH
authors.lastname: Advani
authors.forename: S G
authors.initials: SG
authors.lastname: Gangal
mesh_terms: D000328:Adult; D000818:Animals; D006689:Hodgkin Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000502:physiology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D010835:Phytohemagglutinins
chemical_list: D007376:Interleukin-2; D008222:Lymphokines; D008934:Mitogens; D010835:Phytohemagglutinins; D007371:Interferon-gamma