Human T‐cell leukemia virus type I(HTLV‐I) infection of T cells bearing T‐cell receptor γδ: Effects of HTLV‐I infection on cytotoxicity

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Abstract
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) γδ and functional alterations of the HTLV-I-infected TCR-γδ+ T cells. CD3+CD4−CD8−TCR-γδ+ 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-γδ+ T cells was detected by Southern blot analysis. During the continuous culture of HTLV-I-infected TCR-γδ+ T-cell clones, 2 distinct phases were observed in terms of cytotoxic activity and expression of the CD3-TCR-γδ complex. Early after HTLV-I infection, TCR-γδ+ 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-γδ complex on the cell surface was markedly decreased. Concomitant with the decreased expression of CD3- TCR-γδ 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-γδ+ T cells, and that consequently their functions are profoundly affected through 2 distinct phases.