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 lymphotropic virus type I (HTLV-I) infections, peripheral blood T cell subsets mere analyzed by using a PCR-based assay that permits determination of complementarity-determining region 3 (CDR3) length variation in TCR VP transcripts. In two of four asymptomatic HTLV-I carriers and in four of five patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), mono- or oligoclonal expansions were detected in the CD4(+) T cell subset. 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 expansion 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 number of uninfected individuals. Oligoclonal expansions in the CD8(+) T cell subset were detected in all subjects, including the patient with adult T cell leukemia, No differences in the number of expanded clones were noted between asymptomatic carriers and in patients with HAM/TSP and there was no obvious restriction in the TCR V region usage. Direct sequencing revealed no significant bias in the CDR3 motifs utilized by the predominant clones. This report is the first direct demonstration of clonal expansions within fractionated 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 frequently and independently of disease association.