title: Reduced 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity response in IL-15 receptor alpha-deficient mice correlates with diminished CCL5/RANTES and CXCL10/IP-10 expression.
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 alpha chain (IL-15Ralpha)-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-15Ralpha(-/-) mice. The lower levels of CXCL10/IP-10 suggested that the IL-15Ralpha(-/-) mice had reduced production of IFN-gamma, the primary inducer of CXCL10/IP-10, which was in fact the case. However, by contrast with CCL5/RANTES, the diminished levels of IFN-gamma were likely due to the decreased number of skin-infiltrating CD8(+) T cells, since IFN-gamma production by antigen-stimulated CD8(+) T cells was comparable between wild-type and IL-15Ralpha(-/-) mice. Our data suggest a positive, pro-inflammatory feedback loop involving CCL5/RANTES, IFN-gamma 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-15Ralpha, 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-15Ralpha, indicating that IL-15Ralpha is critical for CCL5/RANTES expression in CD8(+) T cells.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Jia-Perng
authors.initials: JP
authors.lastname: Chen
authors.forename: Nan-Shih
authors.initials: NS
authors.lastname: Liao
authors.forename: Szu-Liang
authors.initials: SL
authors.lastname: Lai
authors.forename: Lilan
authors.initials: L
authors.lastname: Hsu
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Mao
authors.forename: Min-Chi
authors.initials: MC
authors.lastname: Ku
authors.forename: Fang
authors.initials: F
authors.lastname: Liao
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D054357:Chemokine CXCL10; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D019743:Chemokines, CXC / Q000096:biosynthesis*; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000276:immunology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000172:deficiency*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; C508025:Il15ra protein, mouse; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene