FUNCTIONAL PHENOTYPE OF TRANSFORMED HUMAN ALPHA-BETA AND GAMMA-DELTA T-CELLS DETERMINED BY DIFFERENT SUBGROUP-C STRAINS OF HERPESVIRUS SAIMIRI

Based on sequence divergence in the transformation-relevant region, he rpesvirus saimiri strains are classified into three subgroups. Only me mbers of subgroup C transform human T lymphocytes to continuous interl eukin-2-dependent growth in culture, In this study, human cord blood T cells were immortalized bg using different subgroup C strains (C488, C484, and C139), The resulting T-cell lines represented different type s of T-cell clones. They were either CD4(+) or CD8(+) and expressed ei ther the alpha beta or the gamma delta type of T-cell receptors. If tr ansformed 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 diffe rences were observed in T cells immortalized by different subgroup C s trains. Strain C139 persisted at low copy number, compared to the high copy number of prototype C488. The transformation-associated genes st pC and tip of strain C488 were strongly induced after T-cell stimulati on. The homologous genes of strain C139 were only weakly expressed and not induced after activation. After CD2 ligation, the C488-transforme d T cells produced interleukin-2, whereas the C139-transformed cells d id not. Correspondingly, the C139-transformed T cells were less sensit ive to cyclosporin A. Sequence comparison from different subgroup C st rains revealed a variability of the stpC/tip promoter region and of th e Lck-binding viral protein Tip. Thus, closely related subgroup C stra ins of herpesvirus saimiri cause major differences in the functional p henotype of growth-transformed human T cells.