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 inpatients with adult T-cell leuk emia (ATL) and human T-cell leukemia virus type I (HTLV-I) carriers. Howeve r, 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-as sociated myelopathy/tropical spastic paraparesis and ATL using 3-color fluo rescence with CD62L and CD45RA coexpression either with CD4(+) or CD8(+) T cells. The number of naive T lymphocytes was markedly suppressed in patient s with ATL, particularly in those with acute form, compared with uninfected control individuals. The number of naive T cells was low in HTLV-I-infecte d individuals under 50 years old compared with uninfected individuals, wher eas the number of memory T lymphocytes was greater in HTLV-I-infected indiv iduals. 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), wh ich are generated by DNA recombination during early T lymphopoiesis, were q uantified to evaluate thymic function in HTLV-I-infected individuals. TREC levels were lower in HTLV-I-infected individuals than in uninfected individ uals. In HTLV-I carriers less than 70 years old, an increase of Epstein-Bar r 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 control s. These results suggested that the low number of naive T lymphocytes was d ue to suppressed production of T lymphocytes in the thymus, which might acc ount for immunodeficiency observed in HTLV-I-infected individuals. (Blood. 2001;97:3177-3183) (C) 2001 by The American Society of Hematology.