NK1.1+ T cells from IL-7-deficient mice have a normal distribution and selection but exhibit impaired cytokine production

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Abstract
Particular subsets of T cells expressing the NK1.1 antigen have been proposed to play an immune regulatory role by their fast and strong production of cytokines, in particular IL-4. We sought to determine factors driving the functional differentiation of NK1.1+ T cells. Since NK1.1+ T cells are exquisitely sensitive to IL-7 stimulation, we analyzed the development, selection and IL-4 production of NK1.1+ T cells in IL-7 deficient mice (IL-7−/−mice). Besides a sharp reduction of all T cell subsets, NK1.1+ T cells develop at normal relative frequencies in IL-7−/−;mice. They also undergo a normal selection process, as revealed by the biased Vβ TCR repertoire identical to the one in IL-7+/+ mice. However, NK1.1+ T cells from IL-7+/+ mice were found to be impaired in IL-4 and IFN-γ production in in vitro and in vivo models. In addition, IL-7 was able to restore IL-4 production by NK1.1+ thymocytes from IL-7−/− mice. Finally, IL-7 but not IL-4 was able to maintain and increase IL-4 production by NK1.1+ thymocytes from normal mice. These data suggest that the functional maturation of NK1.1+ T cells requires a cytokine-driven differentiation process, in which IL-7 plays a major role.

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