Differential response to genotoxic stress in immortalized or transformed human T-lymphotropic virus type I-infected T-cells

Several alterations in the mechanism of cell cycle control have been observ ed in human T-lymphotropic virus type I (HTLV-I)-infected cells. Here, it i s reported that HTLV-I-infected cells both in their immortalized and transf ormed phase do not undergo apoptosis following ionizing radiation (IR) trea tment. However, when IL-2 withdrawal is combined with genotoxic stress, HTL V-I-infected T-cells in their immortalized phase (IL-2-dependent) undergo a poptosis whereas their transformed counterparts (IL-2-independent) do not. These results suggest that, during the transformation process, the HTLV-I-i nfected T-cells become less sensitive to cell death signals through the acq uisition of constitutive activation of the IL-2 receptor pathway. The expre ssion of bcl-2 and bcl-XL proteins, which, are known to increase cell survi val mediated by IL-2, as well as of p21(waf1) and p53, was not substantiall y different in immortalized and transformed cells following IR, All togethe r, these findings suggest that activation of alternative anti-apoptotic pat hways, regulated by IL-2, might be responsible for the differential cell de ath response observed in immortalized versus transformed HTLV-I-infected T- cells.