Human T-cell leukemia virus type I(HTLV-I) infection of T cells bearing T-cell receptor gamma delta: effects of HTLV-I infection on cytotoxicity.
In order to clarify the cellular tropism of human T-cell leukemia virus type I (HTLV-I) and the effects of HTLV-I infection on T-cell functions, we investigated the infectiousness of HTLV-I on T cells bearing T-cell receptor (TCR) gamma delta and functional alterations of the HTLV-I-infected TCR-gamma delta + T cells. CD3+ CD4-CD8-TCR-gamma delta + T-cell clones which possessed cytotoxicity were co-cultured with a HTLV-I-producing T-cell line. After several weeks, integration of HTLV-I proviral DNA in TCR-gamma delta + T cells was detected by Southern blot analysis. During the continuous culture of HTLV-I-infected TCR-gamma delta + T-cell clones, 2 distinct phases were observed in terms of cytotoxic activity and expression of the CD3-TCR-gamma delta complex. Early after HTLV-I infection, TCR-gamma delta + T cells lost their spontaneous cytotoxicity, but this was restored by the addition of lectin. At this time, no differences were observed in the expression of various surface molecules between HTLV-I-infected and uninfected parent cells, except for increased expression of CD25 on HTLV-I-infected cells. At about 30 weeks after HTLV-I infection, the cytotoxicity of HTLV-I-infected cells was almost completely lost, even in the presence of lectin, and expression of the CD3-TCR-gamma delta complex on the cell surface was markedly decreased. Concomitant with the decreased expression of CD3-TCR-gamma delta complexes, a decrease in the elevation of cytoplasmic Ca2+ concentration induced by anti-CD3 and anti-TCR monoclonal antibodies (MAbs) was also observed. Our present findings thus show that HTLV-I can infect TCR-gamma delta + T cells, and that consequently their functions are profoundly affected through 2 distinct phases.
Yasukawa
M
M
First Department of Internal Medicine, Ehime University School of Medicine, Japan.
Inatsuki
A
A
Yakushijin
Y
Y
Kobayashi
Y
Y
D015703:Antigens, CD / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015490:HTLV-I Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000382:microbiology*; D013997:Time Factors
D015703:Antigens, CD; D016692:Receptors, Antigen, T-Cell, gamma-delta; D002118:Calcium