Figure 1.

Natural killer (NK) cell-mediated control of T cell responses. (A) Stimulus of CD56^bright with IL-2, IL-7, IL-12, IL-15, IL-18, and IL-21 induces cytotoxicity (G) toward previously activated autologous CD4⁺ T cells through the engagement of NKG2D and the natural cytotoxicity receptors (NCRs) (27). (B) Pre-activation of NK cells with IL-2 and of autologous CD4⁺ T cells with staphylococcal enterotoxin B (SEB) induces cytotoxicity of NK cells toward autologous T cells (G) through engagement of the activating receptor DNAM-1 on NK cells and its ligand CD155 on T cells (21). (C) In the presence of the anti-IL-2Rα monoclonal antibody daclizumab, IL-2 signal through the intermediate-affinity receptor induces cytotoxicity of CD56^bright NK cells toward autologous activated CD4⁺ T cells (G) involving the transfer of granzyme K to target cells (23). (D) The pro-inflammatory cytokines IL-12 and IL-15 induce anti-proliferative (H) and cytotoxic function of CD56^bright NK cells toward CD4⁺ T cells undergoing activation through engagement of the NCRs NKp30 and NKp46 and release of granzyme B (25). (E) CD56^bright suppress proliferation of autologous CD4⁺ T cells (H) by releasing adenosine (26). (F) IL-27 induces suppressor function of CD56^bright NK cells toward autologous CD4⁺ T cells (H), which is associated with increased perforin content (9).