Functional phenotype of transformed human alphabeta and gammadelta T cells determined by different subgroup C strains of herpesvirus Saimiri.
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+ or CD8+ and expressed either the alphabeta or the gammadelta type of T-cell receptors. If transformed by the same virus strain, alphabeta and gammadelta 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.
Fickenscher
H
H
Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany. helmutfr@viro.med.uni-erlangen.de
Bökel
C
C
Knappe
A
A
Biesinger
B
B
Meinl
E
E
Fleischer
B
B
Fleckenstein
B
B
Bröker
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D016645:Aotidae; D001483:Base Sequence; D018801:CD2 Antigens / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D006567:Herpesvirus 2, Saimiriine / Q000276:immunology* / Q000302:isolation & purification*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D018801:CD2 Antigens; D010750:Phosphoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2