O'Neil, E; Wickremasinghe, RG; Jackson, T; Grant Prentice, H; Lowdell, MW; (2000) CDSαon human natural killer cells may act as a costimulatory molecule. Blood , 96 (11 PART II)
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A subset of human NK cells, defined as CD56+ve/CD3-ve lymphoid cells capable of non-MHC restricted cytotoxicity, can be isolated from peripheral blood which express the CD8α chain as a homodimer in the absence of the βchain. Previous results from our group have confirmed a role for CD56+/CD8wk+ NK cells in autologous cytotoxicity of myeloid leukaemia cells in patients in remission after chemotherapy. The role of CD8α on these cells is unknown. We have isolated CD56+ve/CD3-ve cells from normal donors and cross-linked CD8α with specific mAbs and polyclonal goat-anti-mouse Ig F(Ab)2. Crosslinking induced intracellular phosphorylation of a 25kD molecule but not intracellular calcium mobilisation and failed to activate the cell as determined by CD69 expression. In a standard re-directed lysis assay with P815 cells as the targets, CDS antibodies were unable to mediate lysis. In contrast, cross-linking CD 16 mobilised intracellular Ca2+, upregulated CD69 and mediated redirected lysis of the NK-insensitive P815 cells. Coincubation of patient-derived CD8+ NK cells with autologous, MHC Classl+ve leukaemic blasts lead to capping of the CDSoat the point of contact and lysis of the blasts which was unaffected by the presence of anti-CDSα mAbs. These results suggest that CD8α ligation, while insufficent alone for NK cell activation, may enhance other activatory signals to overcome NKIR-derived inhibitory signals.
|Title:||CDSαon human natural killer cells may act as a costimulatory molecule|
|UCL classification:||UCL > School of Life and Medical Sciences > SLMS Planning and Performance Unit > SLMS Research Support Centre > Platform Technologies|
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