Immobilized anti-CD3 mAb induces anergy in murine naive and memory CD4(+) T cells in vitro

The induction of non-responsiveness in resting murine CD4(+) T cells was investigated using immobilized anti-CD3 mAb. Incubation of freshly isolated CD4(+) T cells with immobilized anti-CD3 mAb led to apoptosis in 40-60% cells, The surviving cells were profoundly non-responsive to subsequent mitogenic stimulation, The non-responsive state was characterized by a lack of IL-2 production and hyper-responsiveness to added IL-2, but was not explained by further activation-induced cell death, The induction of non-responsiveness was not due to modulation of the TCR-CDS complex, and required partial activation of the T cells in that it was accompanied by an increase in cell size and was inhibited by addition of cyclosporin A. Finally, analysis of anti-CD3-mediated responses in naive and memory CD4(+) T cells, separated on the basis of CD44 expression, showed that both naive and memory T cells have similar sensitivity to immobilized anti-CDS mAb-induced activation, apoptosis and anergy. These results demonstrate that TCR-CD3 engagement on freshly isolated resting CD4(+) naive and memory T cells, in the absence of co-stimulation, as achieved by plastic-immobilized anti-CD3 mAb, induces both anergy and cell death.