IL-2 pretreatment of cloned Th lymphocytes has been demonstrated to render these cells unresponsive to subsequent stimulation through the TCR. These cells remain unresponsive for up to 7 days after removal from IL-2. Cells rendered unresponsive to Ag by pretreatment with IL-2 also demonstrated reduced increases in intracellular calcium ([Ca2+]i) after stimulation, hence this unresponsiveness is believed to result from absence of sufficient [Ca2+]i for activation of lymphokine genes. We have confirmed these observations, and demonstrate that only that portion of the [Ca2+]i increase derived from extracellular sources is inhibited in IL-2 pretreated cells. Further, inositol degradation and diacylglycerol production after stimulation are observed to be markedly reduced in cells rendered unresponsive by IL-2 pretreatment, suggesting that signal transduction leading to cleavage of phosphatidylinositol 4,5-bisphosphate after Ag receptor engagement is incomplete in these cells. However, treatment of IL-2 pretreated cells with AlF4- results in both production of inositol phosphates as well as increased intracellular calcium, suggesting that phospholipase C remains active in these cells. It appears that chronic IL-2 exposure regulates Th activation by inhibiting the signal transduction which follows engagement of the TCR.

This content is only available via PDF.
You do not currently have access to this content.