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 were analyzed by using a PCR-based assay that permits determination of complementarity-determining region 3 (CDR3) length variation in TCR Vbeta 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 Vbeta7 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.
Eiraku
N
N
Laboratory of Medical Virology, The Rockefeller University, New York, NY 10021, USA.
Hingorani
R
R
Ijichi
S
S
Machigashira
K
K
Gregersen
P K
PK
Monteiro
J
J
Usuku
K
K
Yashiki
S
S
Sonoda
S
S
Osame
M
M
Hall
W W
WW
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002353:Carrier State / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells / Q000473:pathology*; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006680:HLA Antigens / Q000032:analysis; D015490:HTLV-I Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000473:pathology*
D006680:HLA Antigens; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta