Clonal expansion within CD4(+) and CD8(+) T cell subsets in human T lymphotropic virus type I-Infected individuals

To investigate the diversity of the T cell repertoire involved in human T l ymphotropic virus type I (HTLV-I) infections, peripheral blood T cell subse ts mere analyzed by using a PCR-based assay that permits determination of c omplementarity-determining region 3 (CDR3) length variation in TCR VP trans cripts. In two of four asymptomatic HTLV-I carriers and in four of five pat ients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/T SP), mono- or oligoclonal expansions were detected in the CD4(+) T cell sub set. In one patient with adult T cell leukemia, a specific clone bearing V beta 7 was detected in the CD4(+) T cell subset. In contrast, clonal expans ion was not observed in the CD4(+) T cell subsets of three individuals with asymptomatic HTLV-II infection or in our previous studies of a large numbe r of uninfected individuals. Oligoclonal expansions in the CD8(+) T cell su bset were detected in all subjects, including the patient with adult T cell leukemia, No differences in the number of expanded clones were noted betwe en asymptomatic carriers and in patients with HAM/TSP and there was no obvi ous restriction in the TCR V region usage. Direct sequencing revealed no si gnificant bias in the CDR3 motifs utilized by the predominant clones. This report is the first direct demonstration of clonal expansions within fracti onated T cell subsets (CD4(+) and CD8(+)) in HTLV-I infections and suggests that 1) clonal expansion of CD4(+) T lymphocytes likely occurs as a direct result of infection and 2) polyclonal CD8(+) T cell expansion occurs frequ ently and independently of disease association.