Activation and activation-driven death of human γ/δ T cells

We have concentrated on three functional aspects of human gamma/delta+ T cells. (1) Peripheral blood gamma/delta+ T cells proliferate at a high frequency in response to heat-killed mycobacteria (M.tb.). We present evidence that the primary response of human gamma/delta+ T cells is restricted to those cells bearing a V gamma 9/V delta 2 receptor. (2) T cells expressing the alpha/beta TCR can be activated through the CD2 antigen via an "alternative" pathway. Activation requires the combined signaling of 2 mAb directed against two distinct epitopes of CD2. In striking contrast, cloned gamma/delta+ T cells are activated by a single immobilized anti-CD2 mAb directed against the sheep E-binding epitope of CD2. Stimulation of cloned gamma/delta+ T cells by a single anti-CD2 mAb results in IL-2 production, proliferation, and triggering of cytolytic effector function. (3) Cloned gamma/delta+ T cells are susceptible to programmed cell death (apoptosis) when stimulated simultaneously by anti-CD3/TCR mAb plus exogenous IL-2. The very same clones are activated, however, by the same stimuli in the absence of exogenous IL-2 (but in the presence of LCL feeder cells). This provides the basis for a model where extensive gamma/delta+ T cell proliferation is negatively regulated by antigen plus IL-2.