Reduced 2,4‐dinitro‐1‐fluorobenzene‐induced contact hypersensitivity response in IL‐15 receptor α‐deficient mice correlates with diminished CCL5/RANTES and CXCL10/IP‐10 expression

• Published in: European journal of immunology 2005-03, Vol.35 (3), p.690-698
• Main Authors: Chen, Jia‐Perng, Liao, Nan‐Shih, Lai, Szu‐Liang, Hsu, Lilan, Mao, Wan‐Yu, Ku, Min‐Chi, Liao, Fang
• Format: Article
• Language: English
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; Chemokine CCL5 - biosynthesis; Chemokine CXCL10; Chemokines; Chemokines - biosynthesis; Chemokines - immunology; Chemokines, CXC - biosynthesis; Contact hypersensitivity; Dermatitis, Contact - immunology; Dinitrofluorobenzene - immunology; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression - immunology; IL‐15 receptor; Immunohistochemistry; Inflammation; Interferon-gamma - analysis; Interferon-gamma - immunology; Male; Mice; Neutrophil Infiltration - immunology; Receptors, Interleukin-15; Receptors, Interleukin-2 - deficiency; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200425577

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.