Herpesvirus saimiri immortalization of αβ and γδ human T-lineage cells derived from CD34+ intrathymic precursors in vitro

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Abstract
Herpesvirus saimiri (HVS), an agent that can infect many human cell types, has been shown to immortalize selectively TCR αβ+CD3+ T lymphocytes. Human T cell precursors defined as CD34+CD3−CD4−CD8− were isolated from thymic samples and exposed to HVS in the presence of either IL-2 or IL-7. Cultures lacking the virus were non-viable by day 15. Test cultures, in contrast, showed a sustained proliferative activity lasting >5 months, allowing the phenotypical and molecular analysis of the cellular progeny. In the presence of IL-7, TCR αβ+ cells with three different phenotypes (mainly CD4+CD8−, but also CD4+CD8+ and CD4−CD8+) were immortalized, whereas no TCR γδ+ cells were recovered. Kinetic studies showed that the expansion of immortalized TCR αβ+ cells was preceded by a gradual loss of CD34+ cells followed by a transient accumulation of two distinct cell subsets: first CD1+CD4+CD3− cells and then CD4+CD8+ thymocytes. This resembles early phenotypic changes occurring during normal intrathymic T cell development. In the presence of IL-2, in contrast, only TCR γδ+ cells were immortalized (mainly CD4−CD8+, but also CD4−CD8−). The results show that HVS can be used to read the CD3+ cellular outcome of T cell differentiation assays, including γδ+ CD4−CD8+, γδ+CD4−CD8−, γβ+CD4+CD8−, γβ+CD4−CD8+ and γβ+CD4+CD8+ T cells. A clear role for different cytokines (IL-2 for γδ+ cells, IL-7 for γβ+ cells) in early T cell commitment was also apparent.

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