Deficient helper cell function as a cause of diminished pokeweed mitogen blastogenic responses in patients with...

An investigation has been made of immunoregulatory T-cell function in the non-Hodgkin's lymphomas by comparing immunoregulation of healthy control and patient peripheral blood lymphocyte blastogenic responses to pokeweed mitogen. Normal mononuclear leukocytes (MNL) had significantly higher responses than patient MNL. MNL were subsequently separated into T- and non-T-cell fractions by differential E-rosette sedimentation for co-culture experiments. When normal non-T-cells and autologous irradiated T-cells were recombined, the mitogenic response again exceeded the response of patient non-T-cells recombined with their own irradiated T-cells. However, when normal non-T-cells were co-cultured with patient irradiated T-cells, the mitogenic response was diminished. Moreover, when patient non-T-cells were co-cultured with normal irradiated T-cells, a normal proliferative response occurred. These differences in non-T-cell response are not simply a result of allogeneic effects, since normal non-T-cell responses were the same regardless of whether autologous or normal allogeneic irradiated T-cells were used as helpers. Furthermore, co-culture of normal non-T-cells simultaneously with autologous irradiated T-cells and patient irradiated T-cells revealed no diminution of blastogenic response compared with co-cultures of normal non-T-plus autologous irradiated T only, suggesting no net suppression by patient irradiated T-cells. Studies with monoclonal antibodies revealed that patient T-cells had normal to increased ratios of OK-T4+:OK-T8+ cells. These results suggest that peripheral blood T-cells from patients with non-Hodgkin's lymphomas, despite the presence of a normal to increased ratio of OK-T4+:OK-T8+ cells, are functionally deficient in their helper capacity for non-T-cell blastogenic response to pokeweed mitogen. Abnormal helper T-cell function may explain some of the immune deficits in patients with non-Hodgkin's lymphoma and may be important in the pathogenesis of these diseases.