Characterization of a Suppressor-Cell Leukemia: Evidence for the Requirement of an Interaction of Two T Cells in the Development of Human Suppressor Effector Cells

To characterize the suppressor activity of neoplastic T cells from a child with acute lymphoblastic leukemia and hypogammaglobulinemia, we applied an in vitro assay that determines the capacity of pokeweed-mitogen-stimulated lymphocytes to mature into immunoglobulin-secreting cells. The geometric mean synthesis by peripheral blood lymphocytes from 12 normal persons was 3200 ng for IgM, 2447 ng for IgG and 1825 ng for IgA (2 X 106 cells per 12 days in culture). The patient's leukemic cells produced no detectable immunoglobulin and depressed the immunoglobulin production of normal lymphocytes by 85 to 100 per cent in co-culture experiments. However, suppression was observed only when co-operating normal T cells were present. Prior irradiation of either the leukemic T cells or the co-operating normal T cells nullified the suppressor effect. Therefore, an interaction between at least two different T-cell subsets may be required for the generation of suppressor effector T cells in man. (N Engl J Med 298:66–72, 1978) NORMAL humoral immunity is based on an intricate network of co-operating lymphocytes and accessory cells. Thymic-derived lymphocytes (T cells) play an important part in the regulation of humoral immune responses by acting as potentiators or inhibitors of the transition of bone-marrow-derived lymphocytes (B cells) into immunoglobulin-secreting plasma cells. The T cells that potentiate this B-cell transition are categorized as helper cells, whereas those that inhibit the transition are categorized as suppressor cells.1 2 3 Help and suppression are mediated by different populations of T cells, each genetically committed to mediate only one of these two functions.4 5 Neoplasms of T-cell origin are of.