Abnormal in vitro proliferation and differentiation of T cell colony-forming cells in patients with tropical spastic paraparesis/human T lymphocyte virus type I (HTLV-I)-associated myeloencephalopathy and healthy HTLV-I carriers.
T cell colonies were generated from the peripheral blood mononuclear cells (PBMC) of 10 patients with tropical spastic paraparesis/human T lymphocyte virus type I (HTLV-I)-associated myeloencephalopathy (TSP/HAM), two healthy HTLV-I carriers, and 17 healthy HTLV-I-seronegative subjects. PBMC were cultured in methylcellulose in the absence of added growth factors (spontaneous T cell colonies), or in the presence of phorbol myristate acetate and interleukin 2 (induced T cell colonies). PBMC T cell colony-forming cells (T-CFC) from all TSP/HAM patients and HTLV-I carriers were able to grow in the absence of added growth factors and/or mitogenic stimulation. Pooled spontaneous and induced colonies were composed of cells bearing CD3+, CD4+, CD8+, and CD1+ antigens. Colonies from normal HTLV-I-seronegative subjects displayed mature cells bearing the CD3+, CD4+, CD8+, and CD1- surface phenotype. In addition, spontaneous and induced T cell colonies expressed HTLV-I antigens in 18-38% of the cells from TSP/HAM patients and HTLV-I carriers. These results demonstrate that HTLV-I infection is associated with an abnormal proliferation and differentiation of T cell progenitors in vitro and that the T-CFC from HTLV-I-seropositive individuals are infected, suggesting that T-CFC abnormalities may play a predominant role in the pathophysiology of HTLV-I.
Lunardi-Iskandar
Y
Y
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Gessain
A
A
Lam
V H
VH
Gallo
R C
RC
D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016827:CD8 Antigens / Q000032:analysis; D002353:Carrier State / Q000382:microbiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D015490:HTLV-I Infections / Q000473:pathology* / Q000503:physiopathology; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015493:Paraparesis, Tropical Spastic / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D013234:Stem Cells / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D013755:Tetradecanoylphorbol Acetate