1991 Fiscal Year Final Research Report Summary
Abnormality of signal Transduction via T-cell receptors mediated by retrovirus infection
| Project/Area Number |
02670283
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Ehime University |
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Principal Investigator |
YASUKAWA Masaki Ehime University School of Medicine, Associate Professor, 医学部, 助教授 (60127917)
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| Co-Investigator(Kenkyū-buntansha) |
INATSUKI Akira Ehime University School of Medicine, Senior Resident, 医学部附属病院, 医員
HORIUCHI Takahiko Ehime University School of Medicine, Assistant Professor, 医学部, 助手 (90219212)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Immunodeficiency / Retrovirus / T-cell receptor / Cytotoxicity / signal transduction |
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| Research Abstract |
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.
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