NK1.1+ T cells from IL-7-deficient mice have a normal distribution and selection but exhibit impaired cytokine production.
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-/-m 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 V beta 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-gamma 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-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.
Vicari
A P
AP
DNAX Research Institute, Palo Alto, CA 94304-1104, USA.
Herbelin
A
A
Leite-de-Moraes
M C
MC
Von Freeden-Jeffry
U
U
Murray
R
R
Zlotnik
A
A
D000818:Animals; D000941:Antigens / Q000032:analysis*; D000950:Antigens, Ly; D000954:Antigens, Surface; D016207:Cytokines / Q000096:biosynthesis* / Q000172:deficiency*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000172:deficiency; D015851:Interleukin-7 / Q000172:deficiency* / Q000235:genetics*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009928:Organ Specificity / Q000276:immunology; D011506:Proteins / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D016207:Cytokines; D015851:Interleukin-7; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D015847:Interleukin-4