Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity

Consistent with their role in host defense, mature dendritic cells (DCs) fr om central lymphoid organs preferentially prime for T helper cell type 1 (T h1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine pro files of activated T cells from mucosal lymph nodes. This study on rat resp iratory tract DCs (RTDCs) provides an explanation for this paradox. We demo nstrate that freshly isolated RTDCs are functionally immature as defined il l vitro, being surface major histocompatibility complex (MHC) IIlo, endocyt osis(hi), and mixed lymphocyte reaction(lo), and these cells produce mRNA e ncoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive tra nsfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-s pecific immunoglobulin (Ig)G(1) responses, and antigen-stimulated splenocyt es from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo Ig G priming capacity by 2-3 logs, inducing production of both Th1- and Th2-de pendent IgG subclasses and high levels of IFN-gamma by antigen-stimulated s plenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocyto sis, MHC II processing associated genes, and IL-10 mRNA expression. Full ex pression of IL-12 p40 required additional signals, such as tumor necrosis f actor alpha or CD40 ligand. These results suggest that the observed Th2 pol arity of the resting mucosal immune system may be an inherent property of t he resident DC population, and furthermore that mobilization of Th1 immunit y relies absolutely on the provision of appropriate microenvironmental cost imuli.