<i>In vitro</i> Lymphocyte Response to Phytomitogens in Untreated and Treated Patients with Hodgkin’s Disease

Abstract

In vitro lymphocyte response to phytohemagglutinin (PHA), concavalin A (Con A), and pokeweed mitogen (PW) was evaluated in untreated and treated patients with Hodgkin’s disease (HD). The responding capacity to PHA was depressed, though not constantly, in the untreated patients compared with the response of lymphocytes from normal individuals. The depression was more evident, at group level, when the cells were stimulated with suboptimal concentrations of PHA. Radiotherapy constantly induced a strong decrease or a complete loss of the responding capacity of the cells which persisted at low levels for many months. Some years after the initial course of treatment, the response was clearly depressed, but it was better in patients in remission than during relapse. Splenectomy did not affect the responding capacity of the cells. The depressive effect induced by chemotherapy was apparently less marked and persistent than that of radiation. Con A-and PW-induced lymphocyte transformation usually paralleled the PHA-induced response. The depressed response to PHA was not due to an inhibitory activity of HD serum. Washed HD lymphocytes in fetal calf serum were not stimulated better than in autologous plasma, nor were HD sera able to depress the response of normal lymphocytes to PHA, Con A, PW, and PPD. Supernatants from HD lymphocytes cultured for 24 h without any stimulant, and extracts of these cells were also unable to affect the response of normal lymphocytes to PHA.

Study of some Immunological Parameters in Untreated Patients with Hodgkin’s Disease

“…[3], Lymphocyte stimulation by PHA. The culture technique has been described in detail in our pre vious paper [21], Mononuclear cells separated from human peripheral blood on a Ficoll-Urovi son gradient were added to the wells of V bottom microtiter plates in a volume of 0.1 rnl of TC 109 medium containing 20% of FCS at the concentra tion of 2 X 106/ml, followed by the addition of 0.1 ml of either medium alone or medium contain ing the appropriate concentration of PHA. The cultures were pulsed after 56 h by 0.5 «Ci of 3H-thymidine and harvested at 72 h by a multiple au tomated sample harvester (Skatron, Lierbyen).…”

“…In our previous work [21], we were unable to demonstrate any significant effect on the lymphocyte response to PHA by serum from patients with HD, that is, in agreement with the results reported from other workers [14,28]. To also exclude the possibility that the usually high number of phagocytic cells contaminating the standard number of cultured lymphocytes could be responsible for the depressed lymphocyte response, in this work we tried to compare the PHA stimulability of normal and patient cell populations before and after removing phagocytic cells by treatment with iron pow der from the Ficoll-Urovison purified lym phocytes.…”

“…Taking into account the group of un treated patients studied in our previous work [21] and those of the present study (on the whole 60 patients), it was possible to also evaluate the relationship between PHA stimulability of cells and histologic pattern of the disease. The results reported in the table III show that the mean response to the suboptimal dose of PHA was greater in the patients with lymphocyte predomi nance (9 cases) than in those with nodular sclerosis (22 cases) and it was greater in pa tients with nodular sclerosis than in those with mixed cellularity (26 cases).…”

“…In a previous paper we studied the lym phocyte response to PHA in distinct groups of untreated patients and patients examined at various intervals since the treatment [21]. In this paper we report the results obtained in a second group of untreated patients with HD by the simultaneous study of several in vitro tests of lymphocyte function.…”

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

“…T cells from patients with Hodgkin's disease appeared at least as effective as normal T cells in helping pokeweed mitogen-induced immunoglobulin production by normal B cells. However, when normal T cells were co-cultured with B cells from patients with Hodgkin's disease, spontaneous IgG synthesis declined, whereas the addition of patient T cells INTRODUCTION Patients with Hodgkin's disease (HD)' frequently have impaired cell-mediated immunity, as demonstrated by anergy to recall skin tests (1), failure of dinitrochlorobenzene sensitization (2), and impairment of in vitro lymphocyte proliferation induced by mitogens (3)(4)(5), recall antigens (6, 7), or allogeneic cells (8).…”