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The dose response curves of purified normal and chronic lymphocytic leukaemic lymphocytes to highly, purified phytohaemagglutinin in 3- and 6-day cultures have been defined. Normal lymphocytes cultured for 3 days were maximally stimulated by low concentrations of phytohaemagglutinin, in the range 0.4 to 1.4 μg phytohaemagglutinin/106 cells/ml. Higher concentrations of phytohaemagglutinin caused no further stimulation. Normal lymphocytes cultured for 6 days showed a progressively greater response to increasing concentrations of phytohaemaggluttnin up to 15 μg phytohaemagglutinin/106 cells/ml. Chronic lymphocytic leukaemic lymphocytes responded subnormally to all ranges of phytohaemagglutinin concentrations tested, m both 3- and 6-day cultures. The shape of the dose response curve resembled the normal curve in 2 of 5 cases of chronic lymphocytic leukaemic lymphocytes studied in 3-day cultures, and in all 7 cases studied in 8-day cultures. No evidence could be adduced of a consistently greater response of chronic lymphocytic leukaemic lymphocytes in 6-day compared with 3-day cultures. Five hours' exposure of normal lymphocytes to an optimum phytohaemagglutinin dose did not result in maximum H³-thymidine incorporation after 3 days in culture. [ABSTRACT FROM AUTHOR]

The underlying basis for hypogammaglobulinaemia in patients with chronic lymphatic leukaemia (CLL) was investigated by measurement of immunoglobulin produced in vitro in cultures of pokeweed mitogen-stimulated B and T lymphocytes. B and T cells were separated by sheep red blood cell rosette techniques and, by culture of these cells from CLL patients in various combinations with B or T cells from normal subjects, it was possible to measure independently the function of B lymphocytes and the helper or suppressor function of T lymphocytes. By these methods it was found that the B lymphocytes of six of eight patients failed to produce immunoglobulins in vitro. B lymphocytes from two patients appeared to produce immunoglobulins in vitro. T lymphocytes from five of the eight patients had low or undetectable helper T cell function and in six patients their T lymphocytes had excessive suppressor activity in comparison to T lymphocyte populations from normal subjects. Whether the primary abnormality in the CLL T cell populations was a deficiency of helper T cells or excess of suppressor T cells was uncertain from these studies. These results suggest that immunoglobulin production by B lymphocytes from most patients with CLL was abnormal but also that T cells from CLL patients may be abnormal in respect to their role in immunoglobulin production at an early stage of the disease. These findings may assist in understanding the pathogenesis of this disease and lead to new approaches in treatment. [ABSTRACT FROM AUTHOR]