Expression of soluble CD137 correlates with activation-induced cell death of lymphocytes.

CD137 is a member of the tumour necrosis factor receptor family which delivers a potent co-stimulatory signal to T lymphocytes. Soluble forms of CD137 (sCD137) can be found at enhanced levels in sera of patients with rheumatoid arthritis. Here we show that expression of sCD137 lags behind that of membrane-bound CD137 (mCD137) by about 24 h. In fully activated lymphocytes, time of maximum increase and level of expression of sCD137 were at day 2 and 3, respectively. Expression of sCD137 in lymphocytes requires strong activation, and levels of sCD137 correlate negatively with lymphocyte proliferation and positively with the degree of activation-induced cell death caused by mitogen overstimulation. Since activation of lymphocytes through membrane-bound CD137 delivers a potent stimulatory signal, sCD137 may provide a negative control mechanism for immune responses.