Basophils Can Directly Present or Cross-Present Antigen to CD8 Lymphocytes and Alter CD8 T Cell Differentiation into IL-10-Producing Phenotypes

Abstract

There is increasing evidence suggesting that basophils play a critical role in developing Th2-type immunity both in vitro and in vivo. We previously reported that basophils cocultured with naive CD4 T cells stimulated with Ag promote the differentiation of the T cells into IL-4-producing Th2 cells. In the present study, we examined the roles of basophils during CD8 T cell activation. Although stimulating OVA-specific OT-I CD8 T cells with OVA peptide-pulsed splenic dendritic cells primarily induced the production of IFN-γ, adding basophils into the coculture induced IL-10 production. Surprisingly, basophils were capable of directly presenting peptide Ag or of cross-presenting protein Ag to CD8 T cells. CD28-mediated costimulation dramatically enhanced T cell IL-10 production, yet neither ICOS nor CD86 was involved in IL-10 production. Basophil-mediated IL-10 induction was greatly diminished without IL-4 or IL-6, indicating that these cytokines are necessary for programming CD8 T cell IL-10 production. Adding IL-4 or IL-6 into CD8/APC coculture was not sufficient to induce IL-10 production; however, the presence of both cytokines significantly induced IL-10 production without basophils. Finally, CD8 T cells producing IL-10 induced by basophils did not display regulatory cell functions. Collectively, these results suggest a novel function of basophils that act as professional APCs to present Ag to CD8 T cells, thus inducing IL-10 production.