Endogenously produced IL-4 strongly enhances CD8+ T cell proliferation and accumulation in homeostatic conditions and during Th2 responses (87.24)

Abstract

Abstract IL-7 and IL-15 have important stimulatory roles in CD8+ T cell homeostasis. We evaluated whether another γc-related cytokine, IL-4, also stimulates CD8+ T cell proliferation and accumulation in vivo. Wild-type (WT) mice have twice as many splenic CD8+ T cells as IL-4- or IL-4Rα-deficient mice, with similar numbers of naïve cells but ~5-fold more memory phenotype cells. WT CD8+ T cells outcompete IL-4Rα-deficient CD8+ T cells following cell transfer and SCID mice reconstituted with equal numbers of WT and IL-4Rα-deficient CD8+ T cells have twice as many splenic WT as IL-4Rα-deficient CD8+ T cells 2 weeks later. WT, but not IL-4Rα-deficient CD8+ T cells proliferate when transferred into IL-4Rα-deficient mice that have been immunized with goat anti-mouse IgD antibody or infected with Nippostrongylus brasiliensis to stimulate a Th2 response. Consistent with this, splenic CD8+ T cell accumulation is entirely IL-4- and IL-4Rα-dependent and proliferation is predominantly IL-4- and IL-4Rα-dependent in mice infected w132th Schistosoma mansoni and pulmonary CD8+ T cell proliferation is rapidly suppressed by anti-IL-4R□ mAb in a mouse model of asthma. Furthermore, even ng quantities of IL-4 stimulate CD8+ T cell proliferation and accumulation in vivo. Thus, IL-4 is a potent, biologically important stimulator of CD8+ T cell proliferation and accumulation in vivo. Supported by the US Dept of Veterans Affairs and NIH.