RESUMEN
Although NK cells were initially described as lymphocytes that lacked the characteristic markers of B and T cells, we now appreciate the plethora of activating and inhibitory receptors that define the NK cell surface phenotype. Recent studies have provided new insights into the molecular mechanisms that drive NK cell development, control the NK cell receptor repertoire and the cytokines that define the NK cell niche. These findings form the basis for an updated model of NK cell differentiation.
Asunto(s)
Diferenciación Celular/fisiología , Células Asesinas Naturales/fisiología , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Citocinas/fisiología , Homeostasis/fisiología , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/fisiología , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Activación de Linfocitos/fisiología , Factores de Transcripción/fisiologíaRESUMEN
Natural killer (NK) cell development is thought to occur in the bone marrow. Here we identify the transcription factor GATA-3 and CD127 (IL-7R alpha) as molecular markers of a pathway of mouse NK cell development that originates in the thymus. Thymus-derived CD127+ NK cells repopulated peripheral lymphoid organs, and their homeostasis was strictly dependent on GATA-3 and interleukin 7. The CD127+ NK cells had a distinct phenotype (CD11b(lo) CD16- CD69(hi) Ly49(lo)) and unusual functional attributes, including reduced cytotoxicity but considerable cytokine production. Those characteristics are reminiscent of human CD56(hi) CD16- NK cells, which we found expressed CD127 and had more GATA-3 expression than human CD56+ CD16+ NK cells. We propose that bone marrow and thymic NK cell pathways generate distinct mouse NK cells with properties similar to those of the two human CD56 NK cell subsets.