Studies of Cell Subpopulations Mediating Mitogen Hyporesponsiveness in Patients with Hodgkin's Disease

Abstract

A B S T R A C T Hodgkin's disease (HD) is associated with a deficit in T-cell immunity characterized by skin test anergy and decreased lymphocyte responses to phytohemagglutinin (PHA). To investigate this mitogen hyporesponsiveness in HD, we separated peripheral blood mononuclear cells on Ficoll-Hypaque gradients and determined their response to various suboptimal concentrations of PHA. As was expected, patients with HD demonstrated marked mitogen hyporesponsiveness relative to normal controls; however, if the cell suspensions were first passed through glass wool columns to remove adherent cells, the PHA responsiveness of the hyporesponsive HD cells was markedly increased. In contrast, the responsiveness of normal controls was decreased so that the responses of nonadherent normal and HD cells were statistically indistinguishable. Evidently, a glass wool-adherent suppressor cell had been removed from patients with HD, while a glass wool-adherent cell which enhanced mitogenic responses had been removed from normal controls during column passage. Previous to column depletion, patients with HD had decreased proportions of E-rosettes and increased proportions of cells with surface a-fetoprotein; however, the proportion of these cells was not changed after column passage. Significant changes with column depletion of glass wool-adherent cells in HD were recorded in the proportions of monocytes (13.2 vs 5.8%) and lymphocytes with C-3 receptors (12.6 vs. 7.8%). The only significant change in normal controls was a decrease in the proportion of monocytes (10 vs. 1.7%). To determine ifglass-adherent cells would have a suppressor effect, HD-adherent cells were added in progressively increasing numbers to mononuclear cell suspensions depleted of glass wool-adherent cells. PHA responsiveness returned Mr.

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

“…Wright's stain of the peripheral blood mononuclear cell preparations revealed 96-98% mononuclear cells, 2-4% polymorphonuclear leukocytes and variable numbers of platelets. Previous work in our laboratory has demonstrated no difference between the adherent and nonadherent population in percentage of cells bearing Fc receptors, C3 receptors, surface immunoglobulin, or cells forming E-rosettes with sheep erythrocytes (11).…”

“…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.…”

Changes in Lymphocyte Activity after Thermal Injury

“…Human T suppressor cells have been demonstrated that are both mitomycin C sensitive and resistant (32)(33)(34). Suppressive monocytes have also been demonstrated in humans and are usually mitomycin resistant (35)(36)(37).…”

Spectrum of immunodeficiencies with Hodgkin's disease.

“…Suppression by a monocytoid cell contributes to the proliferative hyporesponsiveness of lymphocytes from patients with Hodgkin's disease (16)(17)(18)(19). This abnormality is associated with an increase in the number of monocytes relative to lymphocytes in monioniuclear leukocyte (MNL)1 preparations (17).…”