Impaired Lymphocyte Transformation in Ataxia-Telangiectasia in Part Due to a Plasma Inhibitory Factor

Abstract

Abstract Studies of lymphocyte transformation in ataxia telangiectasia (A-T) revealed reduced responses to PHA in 14 of 16 cases, to PWM in eight of 12 cases, and to SLO in seven of 10 cases, when 20% autologous plasma was used in the culture media. It was possible to improve the responses of lymphocytes from 11 of 14 patients with subnormal responses to PHA and from six of eight having reduced responses to PWM by either increasing the concentration of the respective stimulant or by culturing in 20% homologous plasma. When both of these were used simultaneously their beneficial effects were additive. Tenfold increases in the optimal concentrations of PHA and PWM, which were somewhat toxic to normal lymphocytes, resulted in increased tritiated thymidine incorporation by A-T lymphocytes. No significant improvement in the reduced responses to SLO was obtained by either culturing in homologous plasma or by increasing the concentration of this stimulant. Plasma from some A-T patients inhibited the response of normal control lymphocytes to PHA and to a lesser extent to PWM. The relationship of plasma inhibition to the concentration of these stimulants was consistent with a competitive mechanism of action. The sera which inhibited the response of normal cells to PHA and PWM had elevated levels of α2 globulin on paper electrophoresis, which raises the possibility that the inhibitory factor may have this electrophoretic mobility. Although the inhibitory factor accounted in part for the reduced responses to PHA and PWM in approximately 57% of the cases, it did not provide an explanation for the reduced responses in the remaining 25% of the A-T cases with subnormal responses to these stimulants, nor was it shown to contribute to the reduced responses to SLO.