concanavalin-a and aluminum-fluoride

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.

Topics: Aluminum; Aluminum Compounds; Animals; Antigens; Binding, Competitive; Calcium; Clone Cells; Concanavalin A; Diglycerides; Extracellular Space; Fluorides; Glycerides; Immune Tolerance; Inositol Phosphates; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Sugar Phosphates; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer