Non-random expression of CD56 on Vγ2δ2 T cells: Identification of a precursor cytotoxic lymphocyte subset

Abstract

In most lymphocyte subsets, expression of CD56 (neural cell adhesion molecule-1) correlates with cell activation and cytotoxic activity. For T cells bearing the Vgamma2Vdelta2 T cell receptor, isoprenoid pyrophosphate stimulation leads to uniform activation and expansion, but only a fraction of cells express CD56 and display potent cytotoxic activity against tumor cells. We sought to determine whether the development of cytotoxicity among Vgamma2Vdelta2 T cells is random, and therefore a potential property of all cells, or whether it is regulated in a non-random manner, dependent either on antigen recognition properties of specific TCR sequences or the existence of cytotoxic lymphocyte precursors. By tracking the fate of individual cell clones defined by the Vgamma2 chain CDR3 region sequence, we show that CD56 is expressed on precursor cytotoxic T cells already present in the population. The ability to express CD56 was not predicted by TCR sequence, or by the strength of signal received by the TCR, as defined by the proliferation response of individual clones. Although CD56 expression could be induced by cytokine treatment alone, in the absence of expansion, the Vgamma2 repertoire present after cytokine treatment was different from either the ex vivo or phosphoantigen-expanded repertoires, and therefore did not provide a basis for clonotype comparison. For gammadelta T cells, then, cytotoxic effector function requires both proliferative responses to antigen, and a pre-existing capacity for CD56 expression.