Prostaglandin-Producing Suppressor Cells in Hodgkin's Disease

Abstract

We examined the role of a prostaglandin-producing suppressor cell in the hyporesponsiveness to phytohemagglutinin seen in Hodgkin's disease. Addition of indomethacin to phytohemagglutinin cultures of lymphocytes from six patients with Hodgkin's disease resulted in an increase of 182 +/- 60 per cent in 3H-thymidine incorporation versus a 44 +/- 18% increase in 29 controls (mean +/- S.D., P less than 0.001). Without indomethacin the mean response of the lymphocytes in Hodgkin's disease was 48% of that of control. With indomethacin it was 94% of the control value. Phytohemagglutinin cultures of Hodgkin-disease lymphocytes produced approximately fourfold more prostaglandin E2 after 48 hours than did normal lymphocytes (P less than 0.02). Removal of glass-adherent cells markedly decreased the enhancement seen with indomethacin; it reduced prostaglandin E2 production by more than 80% and eliminated the differences in response to phytohemagglutinin between Hodgkin-disease and normal lymphocytes. Thus, a glass-adherent, prostaglandin-producing suppressor cell is responsible for the hyporesponsiveness to phytohemagglutinin seen with Hodgkin-disease lymphocytes.

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

“…In some disease states, however, the suppressor cell is dominant. We have recently reported that glass wool adsorption of mononuclear cells from six patients with Hodgkin's disease resulted in an increased response to mitogens (40). PHA-stimulated cultures of Hodgkin's disease mononuclear cells produced approximately fourfold more PGE2 than normal.…”

“…These cells have been suggested as etiologic or contributory in the pathogenesis of several diseases, including common variable hypogammaglobulinemia (43), IgA deficiency (44), multiple myeloma (45), Hodgkin's disease (11,40,46), and systemic lupus erythematosus (47). Work in this area has been hindered, however, by lack of a suitable assay of suppressor cell activity.…”

Soluble suppressor factors elaborated in experimental malignant ascites

“…Significant immunosuppressive activity was detected in the thymic, splenic, and hepatic cell cultures, but not in cultures of tumor cells. Other workers have shown that these cell suspensions contain populations of suppressor cells capable of secreting prostaglandins ( 15). There are a host of protein and lipoprotein substances in serum capable of suppressing mitogen-induced lymphocyte blastogenesis in vitro (16).…”

Inhibition of interleukin 2 production by prostaglandin E2 is not absolute but depends on the strength of the stimulating signal

“…Prostaglandins are produced by macrophages in the course of immunogenical reactions (reviewed in (1,2)) and are also produced by various types of tumor cells (reviewed in (3)). Patients with Hodgkin's disease have been found to contain prostaglandin-producing suppressor cells which are believed to be responsible for the depressed cellular immunity in these patients (4). It has also been reported that prostaglandins inhibit the rejection of tumors (3,5); and prostaglandin of the E series, PGEl and PGE2, have been shown to inhibit the activation of cytotoxic T lymphocytes (CTL) (6,7).…”

“…It has also been reported that prostaglandins inhibit the rejection of tumors (3,5); and prostaglandin of the E series, PGEl and PGE2, have been shown to inhibit the activation of cytotoxic T lymphocytes (CTL) (6,7). Prostaglandins have been shown to inhibit the proliferative response of lymphoid cells including interleukin-Z dependent cytolytic T-cell lines (8)(9)(10)(11)(12), reviewed in ( 1, 13)); and indomethacin and other inhibitors of prostaglandin synthesis have been shown to enhance the induction of cytotoxic responses against allogeneic cells (10). Recently, prostaglandins of the E type have also been reported to inhibit the production of IL-2 in human lymphocyte preparations (12,14,15).…”