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The Journal of Immunology, 1998, 161: 6674-6680.
Copyright © 1998 by The American Association of Immunologists

Clonal Expansion Within CD4+ and CD8+ T Cell Subsets in Human T Lymphotropic Virus Type I-Infected Individuals1

Nobutaka Eiraku*, Ravi Hingorani{dagger}, Shinji Ijichi{ddagger}, Koichi Machigashira*, Peter K. Gregersen{dagger}, Joanita Monteiro{dagger}, Koichiro Usuku{ddagger}, Shinji Yashiki§, Shunro Sonoda§, Mitsuhiro Osame{ddagger} and William W. Hall2,*

* Laboratory of Medical Virology, The Rockefeller University, New York, NY 10021; {dagger} Department of Medicine, North Shore University Hospital, Manhasset, NY 11030; and {ddagger} Third Department of Internal Medicine and § Department of Virology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan

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 were analyzed by using a PCR-based assay that permits determination of complementarity-determining region 3 (CDR3) length variation in TCR Vß 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 Vß7 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.




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