Cytolytic mechanisms and expression of activation-regulating receptors on effector-type CD8(+)CD45RA(+)CD27(-) human T cells

Circulating CD8(+) T cells with a CD45RA(+)CD27(-) phenotype resemble cytol ytic effector cells because they express various cytolytic mediators and ar e able to execute cytotoxicity without prior stimulation in vitro. We here demonstrate that CD8(+)CD45RA(+)CD27(-) T cells can use both granule exocyt osis and Fas/Fas ligand pathways to induce apoptosis in target cells. The a vailability of these cytolytic mechanisms in circulating T cells suggests t hat the activity of these cells must be carefully controlled to prevent unw anted tissue damage, For this reason, we analyzed the expression of surface receptors that either enhance or inhibit T cell function. Compared with me mory-type cells, effector cells were found to express normal levels of CD3 epsilon and TCR zeta and relatively high levels of CD8, CTLA-4 was absent f rom freshly isolated effector cells, whereas a limited number of unstimulat ed memory cells expressed this molecule. In line with recent findings on CD 8(+)CD28(-) T cells, CD45RA(+)CD27(-) T cells were unique in the abundant e xpression of NK cell-inhibitory receptors, both of Ig superfamily and C-typ e lectin classes. Binding of NK cell-inhibitory receptors to classical and nonclassical MHC class I molecules may inhibit the activation of the cytoly tic machinery induced by either Ag receptor-specific or nonspecific signals in CD8(+)CD45RA(+)CD27(-) T cells.