Natural killer (NK) cells are functionally distinct in their responses to viruses and tumors and in immune regulation. Hence, they have been proposed to mature in a bifurcated fashion analogous to that of type-1 and type-2 T helper cells, which are classified by the profile of cytokines they produce.
Loza and Perussia set out to test the idea that NK cells and T helper cells follow a similar course of differentiation in the acquisition of type-1 or type-2 characteristics. Immature NK cells were isolated from human blood and cultured in the presence of cytokines known to induce either a type-1 or type-2 phenotype. Cell fate was then tracked by using expression of the type-2 cytokine interleukin 13 (IL-13) and the type-1 cytokine interferon g (IFNg) as markers for differentiation. The cytokine IL-4 promoted proliferation of NK precursors into immature type-2 (IL-13) NK cells but did not support their development into an intermediate type-0 (IL-13/IFNg) cell. Instead, this transition was induced by IL-12, which caused these intermediary cells to cease production of IL-13 and to progress to fully functional type-1 (IFNg) NK cells. Thus, all three phenotypes of NK cell may be related by a linear pathway of differentiation. -- SJS
Nature Immunol. 2, 917 (2001).
