INTERLEUKIN-2 PREVENTS PROGRAMMED CELL-DEATH IN ADULT T-CELL LEUKEMIA-CELLS

Adult T-cell leukemia (ATL) is a prototype of the lymphoma/leukemia sy ndromes involving immunologically mature T-lymphocytes. The first retr ovirus described in humans, HTLV-I, is causally related to the disease . In this study, we examined whether ATL cells die in vitro through pr ogrammed cell death (PCD), which has been shown to occur in cells affe cted by several other acute and chronic leukemias. When ATL cells from peripheral blood were cultured in serum-free complete medium, a subst antial proportion of them spontaneously died by PCD. After 48 h of cul ture, approximately 30% of the total DNA was fragmented. Electrophores is indicated that the DNA of the ATL cells had been cleaved into regul ar oligonucleosome fragments each comprising approximately 180 200 bas e pairs. This process was significantly promoted by methylprednisolone and the protein kinase A (PKA) activator Sp-cAMPS in at least some ca ses. Since all ATL cells possess interleukin-2 receptors on the cell m embrane, the effect of IL-2 on spontaneous PCD was assessed. PCD after 48 h of culture was inhibited by 30-50% by 100 U/ml interleukin-2 (IL -2). This effect of IL-2 to prevent spontaneous PCD was dose- and time -dependent. These findings suggest that the viability of ATL cells in vivo is regulated positively and negatively by intrinsic IL-2, glucoco rticoid and regulators of PKA activity. Furthermore, the process of ce ll death may be involved in the development of the disease.