engleski

Altered NK cell development and enhanced NK cell-mediated resistance to MCMV infection 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 virally infected or tumor transformed cells. Although NKG2D is expressed on NK cell precursors (NKPs), it is not known whether NKG2D has any role in NK cell development. Therefore, we have generated NKG2D-deficient mice by targeting the Klrk-1 locus and investigated possible consequences of NKG2D-deficiency on the development, homeostasis and effector functions of NK cells. Here we provide evidence for dual role of NKG2D in the physiology of NK cells: one, rather regulatory, implicated in their development, homeostasis and survival, and, other, important for exerting their effector functions. We observed the following consequences of NKG2D deficiency on the NK cell development and homeostasis: a) faster division of NK cells ; b) perturbation in size of NK cell subpopulations and, c) their augmented sensitivity to apoptosis. As expected, NKG2D-/- NK cells were considerably less responsive to tumor cell targets expressing NKG2D ligands, thus confirming the important role of NKG2D for exertion of their effector functions. NKG2D-/- mice, however, showed an enhanced NK cell-mediated resistance to MCMV infection as a consequence of NK cell dysregulation. In conclusion, we have shown here for the first time, using genetically engineered mouse model, that NKG2D plays an important regulatory role in NK cell development, controlling proliferation, homeostasis and survival of NK cells.

Embryonic stem cells; Gene targeting; Cre/loxP recombination system; NK cell development; NKG2D; NKG2D deficient mice

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