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.