engleski

Altered NK cell Development and Enhanced NK Cell-Mediated Resistance to MCMV in NKG2D-Deficient Mice

NKG2D is a potent activating receptor on NK cells which acts as a molecular sensor for stress exposed cells expressing NKG2D ligands such as infected or tumour transformed cells. Although NKG2D is expressed already on NK cell precursors, its role in NK cell development is still not known. To study impacts of NKG2D on the development, homeostasis and effector functions of NK and other immune cells expressing this receptor, we have generated NKG2D-deficient mice by targeting the Klrk-1 locus. We have found an important regulatory role of NKG2D in the development of NK cells. The absence of NKG2D causes considerably faster division of NK cells, perturbation in size of some NK cell subpopulations and their augmented sensitivity to apoptosis. As expected, NKG2D-/- NK cells are significantly less responsive to tumour cell targets expressing NKG2D ligands, but they retain their reactivity when triggered by other activation receptors or cytokines. NKG2D-/- mice, however, show an enhanced NK cell-mediated resistance to MCMV infection as a consequence of NK cell dysregulation. Altogether, these findings provide evidence for yet unknown regulatory function of NKG2D in NK cell physiology.

NK cells; NKG2D deficient mice

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