Dual functions of PD-1 in CD4+ T cell responses by sublingual mucosa-mediated antigen application (P3210)

Abstract

Abstract [Objective] PD-1 is a co-inhibitory T cell receptor and binds two ligands, B7-H1 and B7-DC. Although the B7-H1:PD-1 pathway is involved in the induction of peripheral tolerance, immunostimulatory effects of B7-H1 or B7-DC have been demonstrated. The sublingual mucosa (slm) has been used as a route for sublingual immunotherapy to induce tolerance against allergens. On the other hand, the slm is also used as vaccination sites to induce immune responses against pathogens. The mechanisms by which slm-mediated immune responses are controlled are unclear. In this study, we investigated the involvement of PD-1 in OVA-specific CD4+ T cell responses by slm-mediated antigen application with and without mucosal adjuvant. [Results and Discussion] CFSE- labeled DO11.10 T cells were transferred into immunodeficient mice and OVA was painted onto slm with or without cholera toxin (CT). In the presence of CT, blockade of PD-1 by mAb or deficiency of PD-1 inhibited Ag-specific CD4+ T cell proliferative responses, whereas without CT, similar PD-1 blockade enhanced the proliferation. PD-1 is comparably induced on Ag-specific T cells with and without CT. Blockade of B7-H1 did not clearly affect T cell responses even in the absence of CT. CT markedly inhibited the induction of B7-H1 in slm DCs. Our results suggest the existence of PD-1-mediated immunostimulatory pathway in the presence of CT. CT may affect the availability of B7-H1 and B7-DC on slm DCs and regulate the dual function of PD-1.