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

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 Ca 2+ 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.