NK1.1(-CELLS FROM IL-7-DEFICIENT MICE HAVE A NORMAL-DISTRIBUTION AND SELECTION BUT EXHIBIT IMPAIRED CYTOKINE PRODUCTION() T)

Particular subsets of T cells expressing the NK1.1 antigen have been p roposed to play an immune regulatory role by their fast and strong pro duction of cytokines, in particular IL-4, We sought to determine facto rs driving the functional differentiation of NK1.1(+) T cells, Since N K1.1(+) T cells are exquisitely sensitive to IL-7 stimulation, we anal yzed the development, selection and IL-4 production of NK1.1(+) T cell s 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 freque ncies in IL-7-/- mice. They also undergo a normal selection process, a s revealed by the biased Vg TCR repertoire identical to the one in IL- 7+/+ mice, However, NK1.1(+) T cells from IL-7-/- mice were found to b e impaired in IL-4 and IFN-gamma production in in vitro and in vivo mo dels. 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-2 or 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.