molein the clonal expansion of lymphocytes and the prolonged survival of CD4-positive cells in vivo. Surviving T-lympho

Clonal proliferation of human T-lymphotropic virus type I (HTLV-I) infected cells has been detected by Southern blot analysis and inverse PCR in patients with adult 1-cell leukemia, patients with HTLV-I-associated diseases, and even in asymptomatic carriers. Combining inverse PCR with long PCR, we amplified the genomic DNA regions flanking the integration sites ofthe HTLV-I provirus to detect clones of infected cells. Inverse long PCR revealed that increased virus load was associated with an increase of both the number of cells in each clone and the number of clones. Clonal proliferations were found in both CD4and CDS-posltive cells in a carrier and a patient with HTLV-I-associated neuropathy/tropical spastic pam paresis. These HTLV-I-infected clones persisted over several years in the same carriers, and, moreover, most of the persistent clones were CD4 positive in a HTLV-I carrier. These findings indicate that HTLV-I infec tion plays an important molein the clonal expansion of lymphocytes and the prolonged survival of CD4-positive cells in vivo. Surviving T-lympho cytes may be susceptible to genetic changes, leading to the onset of leukemia.