A role for the Tec family kinase ITK in regulating SEB induced Interleukin-2 production in vivo via c-jun phosphorylation

It was found that T cells from mice lacking ITK exhibited significantly reduced proliferative responses to SEB exposure in vitro, as well as in vivo. Examination of IL-2 production revealed that ITK null mice produced reduced levels of this cytokine in vitro, and more dramatically, in vivo. In vivo analysis of c-jun phosphorylation, previously shown to be critical for regulating IL-2 production, revealed that this pathway was specifically activated in SEB reactive Vβ8+ (but not non-reactive Vβ6+) T cells from WT mice, but not in Vβ8+ T cells from ITK null mice. However, toxicity analysis indicated that both WT and ITK null animals were similarly affected by SEB exposure.These data show that ITK is required for IL-2 production induced by SEB in vivo, and may regulate signals leading IL-2 production, in part by regulating phosphorylation of c-jun. The data also suggest that perturbing T cell activation pathways leading to IL-2 does not necessarily lead to improved responses to SEB toxicity.Superantigens (SAGs) are microbial toxins of bacterial and viral origin with the ability to activate 5–20% of the T cell population, causing T cell activation, cytokine release and systemic shock [1,2]. Most SAGs share the ability to simultaneously bind the class II major histocompatibility complex molecules and the variable region of the T cell receptor β-chain, without the need to be processed by antigen presenting cells [1,2]. Thus SEB can interact directly with MHC class II molecules on APCs and activate T cells bearing the proper TcR Vβ chains. The result of this interaction is large-scale stimulation of any T cell that expresses the proper TCR Vβ chain. A number of studies have shown that when mice are challenged with a SAG such as Staphylococcal Enterotoxin B (SEB), toxicity results from massive induction of cytokines derived from T-helper-type-1 (TH1) type cells such as IL-2, IFN-γ, TNF-α and TNF-β [1,3]. This cytokine production is accompanied by expansion of the numbers of