Overexpression of IL-15 in vivo enhances Tc1 response, which inhibits allergic inflammation in murine model of asthma

IL-15, a pleiotropic cytokine, is involved in the inflammatory responses in various infectious and autoimmune diseases. We have recently constructed IL-154-transgenic (Tg) mice, which have an increased number of memory-type CD8⁺ T cells in the peripheral lymphoid tissues. In the present study, we found that eosinophilia and Th2-type cytokine production in the airway were severely attenuated in OVA-sensitized IL-15-Tg mice following OVA inhalation. IL-15-Tg mice preferentially developed Tc1 responses mediated by CD8⁺ T cells after OVA sensitization, and in vivo depletion of CD8⁺ T cells by anti-CD8 mAb aggravated the allergic airway inflammation in IL-15-Tg mice following OVA inhalation. Adoptive transfer of CD8⁺ T cells from OVA-sensitized IL-15-Tg mice into normal mice before OVA sensitization suppressed Th2, response to OVA in the normal mice. These results suggest that overexpression of IL-15 in vivo suppresses Th2-mediated-allergic airway response via induction of CD8⁺ T cell-mediated Tc1 response.