Inhibitory NK-cell receptors on T cells: Witness of the past, actors of the future

Inhibitory MHC class I receptors were initially described on natural killer (NK) cells, where they participate in inducing NK-cell self-tolerance. Inhibitory NK-cell receptors (iNKRs) can also be expressed by diverse T-cell subsets, including NKT cells, CD8(+)alphabeta-T-cell receptor (alphabeta-TCR)(+) T cells, CD4(+)alphabeta-TCR+ T cells and gammadelta-TCR+ T cells. Here, we review the factors and the differentiation programme associated with the expression of iNKRs by alphabeta-TCR+ T cells, as well as the consequences of iNKR expression on T-cell function. A selective model for the induction of iNKR(+) T cells is discussed, based on the stochastic expression of various iNKRs by the progeny of a single T-cell clone.