TSLP promotes induction of Th2 differentiation but is not necessary during established allergen-induced pulmonary disease (57.13)

Abstract

Abstract Thymic stromal lymphopoietin (TSLP) has been implicated in allergic inflammation by promoting a Th2-type response. Using in vitro cultures we demonstrated that TSLP played a critical role in the development of Th2 immune responses, but its role on an established Th2 immune environment was not significant. Adoptive transfer of naive DO11.10 ovalbumin (OVA)-specific T cells followed by exposure of OVA showed an early impairment of Th2 immune response in TSLP-/- mice compared to wild type (WT) mice. In contrast, transfer of differentiated Th2 cells into TSLP-/- mice did not change lung pathology or Th2 cytokine production compared to transfer into WT mice. Using a well-established allergen-induced Th2 model demonstrated that there was no difference between WT and TSLP-/- mice. Furthermore, when we treated allergic animals with established disease with a neutralizing anti-TSLP antibody there was no change in airway hyerreponsiveness (AHR) or Th2 cytokine production compared to the control antibody treated animals. Collectively, these studies suggest that in mice TSLP has an important role during the early development of Th2 immune responses. However, TSLP appears to have a minimal role at later stages of allergic disease suggesting that it may not be required for maintaining a persistent and established Th2 immune environment. These studies may offer important data for determining whether targeting TSLP would be beneficial for therapy in established Th2 mediated diseases.