Interleukin 5 Plays an Essential Role in Elicitation of Contact Sensitivity through Dual Effects on Eosinophils and B-1 Cells

Abstract

Background: Elicitation of contact sensitivity (CS) depends on B-1-cell-derived antigen-specific immunoglobulin M (IgM) antibodies that recruit CS effector T cells into the local tissue, which is followed by infiltration of antigen-nonspecific mononuclear cells and polymorphonuclear cells, such as neutrophils and eosinophils. In this study, we investigated the role of interleukin (IL)-5, which has broad effects on both eosinophils and B-1 cells, in elicitation of CS. Methods: IL-5 receptor α-chain-deficient (IL-5Rα–/–) mice and IL-5Rα+/+ mice were contact sensitized with oxazolone hapten. Four days later, mice were challenged with the same hapten, and ear swelling responses were measured at 24 h after challenge. Eosinophil infiltration into the local tissue was determined by examination of skin histology and eosinophil peroxidase activity. To investigate the role of IL-5 in B-1 cell activation, the number of oxazolone-specific IgM-producing cells in the spleen was determined by enzyme-linked immunospot assay. Results: Ear swelling responses in IL-5Rα–/– mice were about half of those in IL-5Rα+/+ mice, and nearly no eosinophil infiltration was observed in IL-5Rα–/– mouse skin. Eosinophil peroxidase activity in the sensitized and challenged IL-5Rα–/– mice was about 11 times less than that in immunized IL-5Rα+/+ mice. Contact sensitization significantly increased in numbers of oxazolne-specific IgM-producing cells in IL-5Rα+/+ mouse spleen, but not in IL-5Rα–/– mouse spleen. Conclusion: We conclude that IL-5-dependent activation of eosinophils and B-1 cells is necessary for induction and elicitation of CS. These findings provide a new insight into complicated mechanisms of CS elicitation and suggest a novel role of IL-5 in the regulation of immune responses.

IL-33 Activates B1 Cells and Exacerbates Contact Sensitivity

“…The process is likely to involve the enhanced IgM response since B1 cell-derived haptenspecific IgM are critically required for the initiation of CS by forming an immune complex and triggering the recruitment of Agspecific T cells (11). Furthermore, IL-5 is required for the elicitation of CS by enhancing B1 and eosinophil functions (44). Our results therefore provide an upstream event by which B1 cells are activated for CS.…”

Itch−/−αβ and γδ T cells independently contribute to autoimmunity in Itchy mice

“…Production of Th2-type cytokines by ␣␤ T cells may well contribute to disease, as IL-5 production has been linked to recruitment of B1 IgM-producing cells to local tissue, which together with eosinophil recruitment can result in contact sensitivity. 53 It is likely that local dysregulation of cytokine production is important for disease induction, and resident innate cells may well be important contributors to this process.…”

Interferon‐γ limits Th1 lymphocyte adhesion to inflamed endothelium: A nitric oxide regulatory feedback mechanism

“…While the reaction to oxazolone is predominantly a Th1-dependent response in which both TNF-a and IFN-c have been shown to play a role, multiple other cytokines such as IL-4, IL-10 and IL-6 have also been shown to participate in this response [26,[35][36][37][38]. Previous studies have suggested that TNF-a is the main inflammatory cytokine, as blockade of TNF-a prevented the CS response, while IFN-c blockade only had a partial protective effect [35,36].…”