INDUCTION OF LONG-TERM BUT REVERSIBLE UNRESPONSIVENESS AFTER ACTIVATION OF MURINE T-CELL HYBRIDOMAS

T cell receptor (TCR)-mediated stimulation of murine T cell hybridomas induces cell activation and lymphokine production. We have observed that following productive activation, T cell hybridomas become refractory to a subsequent stimulation. Hyporesponsiveness is long-lasting but reversible, and is not due to reduced receptor expression. It is noteworthy that hyporesponsiveness is cell autonomous, persists in spite of cell division and does not require continuous exposure to ligands. Hyporesponsive cells retain the ability to produce lymphokines in response to pharmacological agents bypassing receptor triggering, indicating that they possess a functional enzymatic machinery for interleukin 2 synthesis and secretion. Reduced phosphatidylinositol hydrolysis was observed in these cells in response to TCR stimulation, suggesting that hyporesponsiveness result from defective transduction of activation signals. The development of unresponsiveness following receptor stimulation resembles desensitization, and may thus play an important role in the regulation of an immune response and in the induction of immune tolerance.