Mechanisms of NK cell activation: CD4(+) T cells enter the scene

Abstract

Natural killer (NK) cells are innate lymphocytes involved in immunosurveillance through their cytotoxic activity and their capacity to secrete inflammatory cytokines. NK cell activation is necessary to initiate effector functions and results from a complex series of molecular and cellular events. We review here the signals that trigger NK cells and discuss recent findings showing that, besides antigen-presenting cells, T cells can play a central role in the initiation of NK cell activation in lymph nodes.

Fig. 1

CD4⁺ T cell-dependent activation of NK cells in lymph nodes. Upon immunization or infection, DCs present antigen to naïve CD4⁺ T cells in lymph nodes draining the immunization or inoculation sites. This event results in the activation of T cells which secrete IL-2 and upregulate the high affinity IL-2 receptor and CD40L. Activated CD4⁺ T cells contribute to further maturation of DC and their secretion of IL-12. Both cytokines, IL-2 and IL-12, synergize to initiate NK cell activation which results in the secretion of IFN-γ and TNF-α, critical for the development of subsequent adaptive immune responses