Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state.
Opportunistic infections frequently occur in patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) carriers. However, the underlying mechanisms of such infections remain unknown. To clarify the mechanism of immunodeficiency in those infected with HTLV-I, this study analyzed the T-cell subsets in HTLV-I carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis and ATL using 3-color fluorescence with CD62L and CD45RA coexpression either with CD4(+) or CD8(+) T cells. The number of naive T lymphocytes was markedly suppressed in patients with ATL, particularly in those with acute form, compared with uninfected control individuals. The number of naive T cells was low in HTLV-I-infected individuals under 50 years old compared with uninfected individuals, whereas the number of memory T lymphocytes was greater in HTLV-I-infected individuals. Although the increase of memory T lymphocytes correlated with HTLV-I provirus loads, no relationship was found between naive T-cell counts and provirus loads. T-cell receptor rearrangement excision circles (TRECs), which are generated by DNA recombination during early T lymphopoiesis, were quantified to evaluate thymic function in HTLV-I-infected individuals. TREC levels were lower in HTLV-I-infected individuals than in uninfected individuals. In HTLV-I carriers less than 70 years old, an increase of Epstein-Barr virus DNA in peripheral blood mononuclear cells was observed in 6 of 16 (38%) examined, whereas it was detectable in only 1 of 11 uninfected controls. These results suggested that the low number of naive T lymphocytes was due to suppressed production of T lymphocytes in the thymus, which might account for immunodeficiency observed in HTLV-I-infected individuals.
Yasunaga Ji
Department of Internal Medicine II, Kumamoto University School of Medicine, Kumamoto, Japan.
Sakai
T
T
Nosaka
K
K
Etoh Ki
Tamiya
S
S
Koga
S
S
Mita
S
S
Uchino
M
M
Mitsuya
H
H
Matsuoka
M
M
D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002353:Carrier State; D004279:DNA, Viral / Q000032:analysis; D005434:Flow Cytometry; D015490:HTLV-I Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D015851:Interleukin-7 / Q000097:blood; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D015493:Paraparesis, Tropical Spastic / Q000276:immunology; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D019562:Viral Load
D004279:DNA, Viral; D015851:Interleukin-7