HTLV-I efficiently transforms human primary lymphocytes of several varieties to neoplasia both in vivo and in vitro. However, leukemia develops in only a small portion of infected individuals after a long time. Thus, a variety of events in the infected host, including interaction with the immune system and genetic factors, probably play roles in the ultimate pathogenesis of the dis- ease itself. Viral genes, particularly the tax gene, are capable of transactivating a variety of host cell genes, some of which are listed in Table 12.11. Notably, the genes transactivated include interleukin-2 (IL-2) and its receptors (IL-2Rα). This lymphokine (Chapter 18) working through its receptor is a critical growth factor for the lymphoid cells infected by the virus. Thus, the virus, in addition to transactivating many other genes, some of which are important in cell repli- cation (PCNA, c-fos), places the cell in an autocrine mode of growth, i.e. producing both the growth factor IL-2 and its receptor within the same cell. In addition, Yoshida (1996) has pre- sented evidence that the Tax protein is involved in binding to specific nuclear factors involved in cell cycle function. The virus integrates into the host genome randomly (Ohshima et al., 1998) and in so doing appears to induce substantial chromosomal abnormalities. However, because of the extended latent period of viral existence within the genomes of host cell lymphocytes and no obvious neoplastic expression, the viral infection may act initially as a promoting agent over an extended period, ultimately resulting in a transition to the stage of tumor progression and neo- plasia. Preclinical studies in animal models involving lower primates and rabbits have suggested the feasibility of an HTLV-I vaccine, but as yet no human trials to test the efficacy of such vac- cines have been undertaken (cf. IARC, 1996).