Studies of protein phophatases on immune response in normal and autoimmune disease mice.

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Activities of protein phophatases PP1 and PP2A were determined in T and B Iymphocytes of autoimmune-prone MRL/MpJ-1pr/1pr mice (MRL/1pr mice) and two control strains, MRL/MpJ-+/+ mice (MRL/+/+ mice) and C3H/HeJ mice. Potential PP1 activity, which was measured after treatment of lymphocytes with Co^<2+>-trypsin, was much higher in T lymphocytes than B lymphocytes. However, no difference in the activity was observed between MRL/1pr mice and the controls. Spontaneous PP2A activity showed similar levels in T and B lymphocytes from normal mice but potential PP2A activity which was measured after treatment with 2-mercaptoethanol, was significantly higher in T lymphocytes from MRL/1pr mice than those from controls. No differences were detected in PP1 or PP2A activities in B lymphocytes.In the IL-2-dependent murine cytotoxic T cell line CTLL-2, IL-2 induced a rapid and transient decrease in Co^<2+>-trypsin-treated activity of protein phosphatase PP1. The PP1 activity declined to a minimum level, being 70% of control value within 45 min. The decrease of PP1 activity was dependent on IL-2 concentration, and occured specfically in cytosolic fraction. Similar alteration was observed in IL-2 sensitive murine T-lymphoblasts. Neither activity of protein phophatase PP2A nor PP2C showed alteration during the IL-2 stimulation. These results suggest that PP1 plays an important role in early events of the intracellular growth signaling through the IL-2 receptor.