Kazuo Sugamura , Shin - Ichi Nakai , Masahiro Fujii , And

Human T cell leukemia virus (HTLV), which we previously called adult T cell leukemia virus (ATLV), is a possible causative agent of human adult T cell leukemia (ATL) (1). Since the HTLV genome was demonstrated not to contain a typical v-onc gene (2) and the HTLV proviral genome is integrated into random sites in cellular DNA of leukemia cells in each ATL patient (3), the mechanism of HTLV-induced oncogenesis is still unknown. The interleukin 2 (IL-2) autocrine hypothesis can be excluded as the mechanism of ATL leukemogenesis, because the IL-2 receptor (IL-2R) was detected in all ATL leukemia cells and HTLV-transformed human T cells that were examined (4), but the IL2 gene was not transcribed in most of these cells (5). However, it was reported (6) that expression of the IL-2R is abnormal in ATL leukemia cells because it is not down-regulated by anti-IL-2R (Tac) antibody, and is constitutive, while IL2R expression in peripheral blood leukocytes (PBL) stimulated with concanavalin A is down-regulated. This observation resulted in another hypothesis, that the constitutive expression of the IL-2R may play a crucial role in ATL leukemogenesis. Our recent observation (7) that HTLV can induce expression of the IL-2R on human B cell lines, strongly supports the notion that HTLV directly contributes to the constitutive production of the IL-2R on ATL leukemia cells and other HTLV-carrying human T cells. However, it is still unknown how the cell growth signal can be transduced constitutively from the IL-2R expressed on ATL leukemia cells and HTLV-transformed cell lines. Similarly, it has been demonstrated (8) that the A431 human epidermoid carcinoma cell line has a large number of receptors for the epidermal growth factor (EGF) that could be products of the c-erbB gene, a cellular oncogene, and it is suggested (8) that overproduction or uncontrolled expression of the EGF receptors could be related to the appearance of the transformed phenotype in the A431 cell line. We previously (4) obtained HTLV-carrying human T cell lines of two distinct types with respect to their IL-2 dependency. One type (ILT) is IL-2 dependent; the other (TL) is IL-2 independent for in vitro growth. Most of the IL-2independent TL cell lines arose spontaneously from IL-2-dependent ILT cell lines in vitro. This change from IL-2 dependence to IL-2 independence could be due to immortalizing transformation of the cells induced by HTLV (9, 10).