Herpesvirus saimiri immortalization of {alpha}{beta} and {gamma}{delta} human T-lineage cells derived from CD34+ intrathymic precursors in vitro |
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Authors: | Pacheco-Castro Alberto; Marquez Carlos; Toribio Maria L; Ramiro Almudena R; Trigueros Cesar; Regueiro Jose R |
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Institution: | Inmunologfa, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain
1 Centro de Biologfa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma, 28049 Madrid, Spain. |
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Abstract: | Herpesvirus saimiri (HVS), an agent that can infect many humancell types, has been shown to immortalize selectively TCR ß+CD3+T lymphocytes. Human T cell precursors defined as CD34+CD3–CD4–CD8–were isolated from thymic samples and exposed to HVS in thepresence of either IL-2 or IL-7. Cultures lacking the viruswere non-viable by day 15. Test cultures, in contrast, showeda sustained proliferative activity lasting >5 months, allowingthe phenotypical and molecular analysis of the cellular progeny.In the presence of IL-7, TCR ß+ cells with three differentphenotypes (mainly CD4+CD8–, but also CD4+CD8+ and CD4–CD8+)were immortalized, whereas no TCR + cells were recovered. Kineticstudies showed that the expansion of immortalized TCR ß+cells was preceded by a gradual loss of CD34+ cells followedby a transient accumulation of two distinct cell subsets: firstCD1+CD4+CD3– cells and then CD4+CD8+ thymocytes. Thisresembles early phenotypic changes occurring during normal intrathymicT cell development. In the presence of IL-2, in contrast, onlyTCR + cells were immortalized (mainly CD4–CD8+, but alsoCD4–CD8–). The results show that HVS can be usedto read the CD3+ cellular outcome of T cell differentiationassays, including + CD4–CD8+, +CD4–CD8–, ß+CD4+CD8–,ß+CD4–CD8+ and ß+CD4+CD8+ T cells.A clear role for different cytokines (IL-2 for + cells, IL-7for ß+ cells) in early T cell commitment was alsoapparent. |
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Keywords: | Herpesvirus saimiri immortalization T cell precursors thymocyte |
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