Our expectation is that the balance of immunoglobulin isotype response (IgE, IgG, and IgG4) is reflective of the antigen-specific immune response and will occur over time. We anticipate an increase in T regulatory specific cytokines, such as IL-10 and TGF-beta, that will parallel early clinical responses and that may indicate immune deviation toward tolerance. The conversion from Th2 to Th1 cytokine responses would have a similar clinical effect of making a subject less sensitive to tree nuts, but this would likely occur through an alternative mechanism or a mechanism combining T regulatory activation with other T cell changes. A change in basophil activation would indicate that subjects would be less sensitive to a specific tree nut, and we anticipate that response would be in parallel to the finding of clinical desensitization but may not indicate clinical tolerance development. Overall, we will assess these immune parameters over time and in conjunction with clinical levels of reactivity to determine which mechanism(s) is relevant for effective walnut OIT.