IL-9(+) IL-10(+) T cells link immediate allergic response to late phase reaction

Abstract

The mechanism underlying late-phase allergic reactions (LPR) remains incompletely understood. This study aimed to investigate the role of a newly described subset of T cells, interleukin (IL)-9(+) IL-10(+) T cells, in the pathogenesis of LPR. Using a T helper type 2 (Th2) inflammatory mouse model, we examined the frequency of IL-9(+) IL-10(+) T cells in the jejunum by immunohistochemistry. The LPR in the jejunum was observed afterwards. The cytokine profile of IL-9(+) IL-10(+) T cells was characterized and the major cytokine that plays the critical role in the initiation of LPR was investigated. Abundant IL-9(+) IL-10(+) T cells as well as inflammatory cell extravasation in the jejunal sections were observed in sensitized mice 48 h after specific antigen challenge. IL-9(+) IL-10(+) T cells expressed high levels of macrophage inflammatory protein 1 (MIP1) that could be enhanced by T cell receptor activation. MIP1 facilitated macrophage extravasation in local tissue. Macrophage-derived MIP2 contributed to neutrophil infiltration in the intestine in LPR. Pretreatment with anti-MIP antibody inhibited the LPR in the intestine. IL-9(+) IL-10(+) T cells play an important role in LPR. This subset of T cells has the potential to be a novel therapeutic target in the treatment of LPR and LPR-related inflammation.