Control of CD56 expression and tumor cell cytotoxicity in human Vgamma2Vdelta2 T cells

Background: In lymphocyte subsets, expression of CD56 ( neural cell adhesion molecule-1) correlates with cytotoxic effector activity. For cells bearing the V gamma 2V delta 2 T cell receptor, isoprenoid pyrophosphate stimulation leads to uniform activation and proliferation, but only a fraction of cells express CD56 and display potent cytotoxic activity against tumor cells. Our goal was to show whether CD56 expression was regulated stochastically, similar to conventional activation antigens, or whether CD56 defined a lineage of cells committed to the cytotoxic phenotype.Results: Tracking individual cell clones defined by their V gamma 2 chain CDR3 region sequences, we found that CD56 was expressed on precursor cytotoxic T cells already present in the population irrespective of their capacity to proliferate after antigen stimulation. Public T cell receptor sequences found in the CD56+ subset from one individual might appear in the CD56- subset of another donor. The commitment of individual clones to CD56+ or CD56- lineages was stable for each donor over a 1 year interval.Conclusion: The ability to express CD56 was not predicted by TCR sequence or by the strength of signal received by the TCR. For gamma delta T cells, cytotoxic effector function is acquired when cytotoxic precursors within the population are stimulated to proliferate and express CD56. Expression of CD56 defines a committed lineage to the cytotoxic phenotype.