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 Vgamma2Vdelta2 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 Vgamma2 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.


CONCLUSIONS
The ability to express CD56 was not predicted by TCR sequence or by the strength of signal received by the TCR. For gammadelta 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.
Urban
Elizabeth M
EM
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. eurba001@umaryland.edu
Li
Haishan
H
Armstrong
Cheryl
C
Focaccetti
Chiara
C
Cairo
Cristiana
C
Pauza
C David
CD
D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019002:CD56 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D011106:Polyisoprenyl Phosphates / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000943:Antigens, Differentiation; D019002:CD56 Antigen; D011106:Polyisoprenyl Phosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta