IL-9 is involved in various T cell-dependent inflammatory models including colitis, encepahlitis and asthma. However, the regulation and specificity of IL-9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed this question using two different models: experimental colitis induced by transfer of naive CD4 CD45RB T cells into immunodeficient mice, and OVA-specific T cell activation. In the colitis model, constitutive IL-9 expression exacerbated inflammation upon transfer of CD4 CD45RB T cells from wild-type but not from Il9r mice, indicating that IL-9 acts directly on T cells. Suprisingly, such naïve CD4 CD45RB T cells failed to express the Il9r or respond to IL-9 in vitro, in contrast with CD4 CD45RB T cells. By using OVA-specific T cells, we observed that T cells acquired the capacity to respond to IL-9 along with CD44 upregulation, after long-lasting (5 to 12 days) in vivo antigenic stimulation. Il9r expression was associated with Th2 and Th17 phenotypes. Interestingly, in contrast to the response IL-2, antigen restimulation downregulated IL-9 responsiveness. Taken together, our results demonstrate that IL-9 does not act on naïve T cells but that IL-9 responsiveness is acquired by CD4 T cells after in vivo activation and acquisition of memory markers such as CD44. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.