Impaired Cell-Mediated Immunity in Hodgkin's Disease Mediated by Suppressor Lymphocytes and Monocytes

Abstract

A B S T R A C T In Hodgkin's disease a possible mechanism for impaired cellular immunity is cell-mediated suppression, defined as the inhibitory interaction between suppressor cells and effector lymphocytes. To test for the presence of suppressor cells in peripheral blood, we have modified the standard, one-way mixed lymphocyte culture by adding mitomycin C-treated mononuclear cells from the responder. Suppression, expressed as a percent of the base-line mixed lymphocyte culture in which these extra cells are not present, results in a reduction of thymidine incorporated in the modified culture (i.e., 100% suppression = no net thymidine incorporation; 0% suppression = identical thymidine incorporation in both the modified and baseline cultuLre).Suppression was found to be significantly increased in patients with both active Hodgkin's disease (78 ±4.6%) and remission Hodgkin's disease (58±9.3%) compared to normal individuals (21±6.9%) (mean ±+SE). The degree and frequency of suppression were not influenced by disease stage or prior therapy. Cell purification techniques revealed (in 10 patients studied) the suppressor cell to be a monocyte in 6, and a thymus-derived lymphocyte in 4. Possible genetic restriction of the suppressor cell interaction was indicated by a failure of suppressor cells to alter the response of lymphocytes from unrelated individuals, but suppression was obtained with lymphocytes from a histocompatible sibling. Although mononuclear cells from normal individuals suppress less frequently than cells from patients with Hodgkin's disease, normals may demonstrate suppression comparable to that observed in Hodgkin's patients. This finding suggests

Reduced relative dose intensity of primary chemotherapy does not influence prognosis of patients with Hodgkin lymphoma

“…ABVD, various hybrid or alternative regimens) as well. The major reasons are infections resulting not only from neutropenia that is usually less pronounced during standard therapy, but also from the immunodeficiency of HL patients 6 . Thus, the relative dose intensity (RDI) of primary chemotherapy can be reduced in a significant proportion of patients, even those in the early stage of disease and treated with less intensive protocols.…”

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).…”

“…It has been suggested that monocytes release excessive amounits of prostaglandins, thereby causing suppression (20). A second form of suppression, spontaneously effected by T lymphocytes, has been described with Hodgkini's disease (19,21).…”

Increased monocyte-mediated antibody-dependent cellular cytotoxicity (ADCC) in Hodgkin's disease

“…Two of the 3 patients with the highest 51Cr release/103 NSE+ cells (Figure) were in a clinically inactive state of the disease. In contrast, a correlation has been reported between enhanced monocyte suppressor cells and disease activity (Hillinger & Herzig, 1978).…”

“…Urbanitz et al (1975) found reduced phagocytosis in patients with advanced HD and Leb & Merritt (1978) described decreased monocyte chemotactic response and monocyte bactericidal activity in that disorder. Recently, monocyte suppressor function was found to be significantly higher in HD, possibly impairing cellular immunity (Hillinger & Herzig, 1978).…”