Functional phenotype of transformed human alpha beta and gamma delta T cells determined by different subgroup C strains of herpesvirus saimiri

• Published in: Journal of virology 1997-03, Vol.71 (3), p.2252-2263
• Main Authors: Fickenscher, H, Boekel, C, Knappe, A, Biesinger, B, Meinl, E, Fleischer, B, Fleckenstein, B, Broeker, B M
• Format: Article
• Language: English
• Subjects: herpesvirus saimiri
• ISSN: 0022-538X
• DOI: 10.1128/JVI.71.3.2252-2263.1997

Based on sequence divergence in the transformation-relevant region, herpesvirus saimiri strains are classified into three subgroups. Only members of subgroup C transform human T lymphocytes to continuous interleukin-2-dependent growth in culture. In this study, human cord blood T cells were immortalized by using different subgroup C strains (C488, C484, and C139). The resulting T-cell lines represented different types of T-cell clones. They were either CD4 super(+) or CD8 super(+) and expressed either the alpha beta or the gamma delta type of T-cell receptors. If transformed by the same virus strain, alpha beta and gamma delta clones were similar with respect to viral persistence, virus gene expression, proliferation, and Th1-type cytokine production. However, major differences were observed in T cells immortalized by different subgroup C strains. Strain C139 persisted at low copy number, compared to the high copy number of prototype C488. The transformation-associated genes stpC and tip of strain C488 were strongly induced after T-cell stimulation. The homologous genes of strain C139 were only weakly expressed and not induced after activation. After CD2 ligation, the C488-transformed T cells produced interleukin-2, whereas the C139-transformed cells did not. Correspondingly, the C139-transformed T cells were less sensitive to cyclosporin A. Sequence comparison from different subgroup C strains revealed a variability of the stpC/tip promoter region and of the Lck-binding viral protein Tip. Thus, closely related subgroup C strains of herpesvirus saimiri cause major differences in the functional phenotype of growth-transformed human T cells.