Abnormality of signal Transduction via T-cell receptors mediated by retrovirus infection

为了阐明人类逆转录病毒感染介导的免疫缺陷机制，我们研究了成人T细胞白血病的病原体--人类嗜T淋巴细胞病毒I型（HTLV-I）感染后T细胞功能的变化。建立了单纯疱疹病毒特异性CD 4+和CD 8+人细胞毒性T细胞（CTL）克隆和T细胞受体-γ δ + T细胞克隆。通过与产生HTLV-I的T细胞系共培养，用HTLV-I感染这些克隆。在HTLV-1感染的T细胞克隆的连续培养过程中，观察到细胞毒活性和CD 3-TCR复合物表达的两个不同阶段。在HTLV-I感染后早期，CTL失去了它们的细胞毒活性，但通过加入凝集素可以恢复。此时，除了HTLV-1感染的细胞上CD 25的表达增加之外，在HTLV-1感染的和未感染的亲本细胞之间没有观察到各种表面分子表达的差异。另一方面，在HTLV-I感染后的后期，即使在凝集素存在下，HTLV-I感染的细胞的细胞毒性几乎完全丧失，并且细胞表面上的CD 3-TCR复合物的表达显著降低。随着CD 3-TCR复合物表达的减少，抗CD 3和抗TCR单克隆抗体诱导的胞浆Ca ~（2+）浓度升高也减少。因此，我们目前的研究结果表明，T细胞功能受到HTLV-I感染的深刻影响，至少有两个不同的阶段。

In order to clarify the mechanism of immunodeficiency mediated by human retrovirus infection, we investigated the functional alterations of T cells following infection with human T lymphotropic virus type I (HTLV-I), which is the causative agent of adult T-cell leukemia. Herpes simplex virus-specific CD4+ and CD8+ human cytotoxic T-cell (CTL) clones and T-cell receptor-gammadelta + T-cell clones were established. These clones were infected with HTLV-I by co-culture with a HTLV-I-producing T cell line. During the continuous culture of HTLV-I-infected T-cell clones, two distinct phases were observed in terms of cytotoxic activity and expression of the CD3-TCR complex. Early after HTLV-I infection, CTL lost their cytotoxic activity, 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. On the other hand, late 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 complex on the cell surface was markedly decreased. Concomitant with the decreased expression of CD3-TCR complex, a decrease in the elevation of cytoplasmic Ca2+ concentration induced by anti-CD3 and anti-TCR monoclonal antibodies was also observed. Our present findings thus show that T-cell functions are profoundly affected by HTLV-I infection through at least two distinct phases.