Transfer of in vivo primed transgenic T cells supports allergic lung inflammation and FIZZ1 and Ym1 production in an IL-4Rα and STAT6 dependent manner

In this study, we monitored the activation and proliferation status of adoptively transferred allergen-specific na？ve or in vivo primed CD4+ T cells. We found that both the na？ve and in vivo primed T cells expressed similar levels of CD44 and IL-4. However, in vivo primed T cells underwent reduced proliferation in a lymphopenic environment when compared to na？ve T cells. We then used these in vivo generated effector T cells in an asthma model. Although there was reduced inflammation in mice lacking IL-4Rα or STAT6, significant amounts of eosinophils were still present in the BAL and lung tissue. Moreover, specific AAM proteins YM1 and FIZZ1 were expressed by epithelial cells, while macrophages expressed only YM1 in RAG2-/- mice. We further show that FIZZ1 and YM1 protein expression in the lung was completely dependent on signaling through the IL-4Rα and STAT6. Consistent with the enhanced inflammation and AAM protein expression, there was a significant increase in collagen deposition and smooth muscle thickening in RAG2-/- mice compared to mice deficient in IL-4Rα or STAT6.These results establish that transfer of in vivo primed CD4+ T cells can induce allergic lung inflammation. Furthermore, while IL-4/IL-13 signaling through IL-4Rα and STAT6 is essential for AAM protein expression, lung inflammation and eosinophilia are only partially dependent on this pathway. Further studies are required to identify other proteins and signaling pathways involved in airway inflammation.CD4+ T helper type 2 (TH2) cytokines such as IL-4, IL-5 and IL-13 play a critical role in inducing allergy and asthma. These cytokines act on multiple cells types to initiate and propagate the hallmark features of asthma such as pulmonary inflammation, periodic narrowing of airways and mucus hypersecretion [1-7]. Experiments with mice deficient in these cytokines and studies in asthma patients have confirmed these findings [8-10]. Also, the fact that TH2 cells are required in this disease setting ha