T Cell Receptor and Co-Stimulatory Signals for Th9 Generation

In vitro polarization of naïve CD4⁺ T cells toward distinct T helper lineages is crucial for establishing the factors and features that determine the differentiation, stability, and effector function for each T helper subsets. In this regard, the recently defined Th9 subset has been reported with two essential cytokines requirement for their generation. Generating Th9 cells in vitro from naïve CD4⁺ T cells requires the combination of TGF-β and IL-4. However, the amount of IL-9 producing under these minimal conditions is often small. The intent of this chapter is to provide examples to increase the generation of IL-9 producing T cells in vitro by modulating TCR strength and co-stimulation through the TNF family member TL1A. We hope that these methods to efficiently differentiate naïve CD4⁺ T cells toward IL-9 producing cells will facilitate understanding the differentiation and function of Th9 cells and their pathogenesis in various inflammatory and autoimmune diseases.