SEARCH

SEARCH BY CITATION

Keywords:

  • Chemokines;
  • IL-15 receptor;
  • Contact hypersensitivity;
  • Inflammation

Abstract

Using a model of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity (CHS) we found that, as compared with wild-type mice, IL-15 receptor α chain (IL-15Rα)-deficient mice showed significantly less ear swelling. This decreased response was associated with diminished expression of CCL5/RANTES and CXCL10/IP-10, chemokines critical for effector cell recruitment, in the inflamed tissue. We determined that both the number of CD8+ T cells infiltrating the affected skin and the production of CCL5/RANTES by antigen-stimulated CD8+ T cells were decreased in IL-15Rα–/– mice. The lower levels of CXCL10/IP-10 suggested that the IL-15Rα–/– mice had reduced production of IFN-γ, the primary inducer of CXCL10/IP-10, which was in fact the case. However, by contrast with CCL5/RANTES, the diminished levels of IFN-γ were likely due to the decreased number of skin-infiltrating CD8+ T cells, since IFN-γ production by antigen-stimulated CD8+ T cells was comparable between wild-type and IL-15Rα–/– mice. Our data suggest a positive, pro-inflammatory feedback loop involving CCL5/RANTES, IFN-γ and CXCL10/IP-10 that underlies the CHS reaction and that is disrupted, likely primarily by a defect in CCL5/RANTES production, in mice lacking IL-15Rα, resulting in impaired leukocyte recruitment and inflammation. Moreover, it is particularly noteworthy that the defect in CCL5/RANTES expression in CD8+ T cells is intrinsic to the absence of IL-15Rα, indicating that IL-15Rα is critical for CCL5/RANTES expression in CD8+ T cells.