Preferential contribution of B7‐H1 to programmed death‐1‐mediated regulation of hapten‐specific allergic inflammatory responses

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Abstract
Programmed death‐1 (PD‐1) and its ligands, B7‐H1/PD‐L1 and B7‐DC/PD‐L2, are new CD28‐B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten‐induced contact hypersensitivity (CH). Administration of anti‐PD‐1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti‐B7‐H1 mAb, but not anti‐B7‐DC mAb, also enhanced CH reactions. The anti‐PD‐1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7‐H1 was induced on activated T cells and antigen‐presenting cells (APC) in the skin and the DLN, whereas B7‐DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7‐H1+B7‐DC–CD86low, was found in sensitized DLN. The blockade of B7‐H1, but not B7‐DC, dramatically enhanced the initial T cell proliferative responses against hapten‐pulsed DLN APC, suggesting the preferential contribution of B7‐H1 to the T cell‐APC interaction. Our results demonstrate the regulatory role of PD‐1 and the differential roles of B7‐H1 and B7‐DC in hapten‐induced immune responses. The PD‐1‐B7‐H1 pathway may play a unique role in regulating inflammatory responses.