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

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 -CD86 low , 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.

SHP-1 and SHP-2 Associate with Immunoreceptor Tyrosine-Based Switch Motif of Programmed Death 1 upon Primary Human T Cell Stimulation, but Only Receptor Ligation Prevents T Cell Activation

“…In doing so, we demonstrated that PD-1 ligation had no costimulatory activity and was very efficient in preventing suboptimal CD3/28 costimulation from inducing T cell proliferation and cytokine production. These data add to the growing body of evidence that direct ligation of PD-1 inhibits T cell activation (43)(44)(45)(46).…”

Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

“…PMA was purchased from Sigma-Aldrich, and ionomycin and PP2 from EMD. Anti-mPD-L1 (MIH5) was previously described (Tsushima et al, 2003). B cell hybridomas producing anti-mCD3 (145-2C11) and anti-mCTLA-4 (UC10.4F10.11) were provided by J. Bluestone (University of California, San Francisco, CA); anti-mCD28 (PV-1) by R. Abe (Science University of Tokyo, Tokyo, Japan); anti-mTCR- (H57-597) by R.T. Kubo (Cytel Corp., San Diego, CA); anti-H-2K b (20-8-4) by N. Shinohara (Kitasato University, Tokyo, Japan); and anti-I-E k (14-4-4), antimCD80 (16-10A1), anti-mICAM-1 (YN1/1.7.4), and anti-I-E k in complex with MCC88-103 (D4; Reay et al, 2000) by M.L.…”

Programmed Death-1 Pathway in Host Tissues Ameliorates Th17/Th1-Mediated Experimental Chronic Graft-versus-Host Disease

“…Neutralizing mAbs against mouse PD-1 (RPMI-14), PD-L1 (MIH6), and PD-L2 (TY25) for in vivo experiments were prepared as described previously (10,14,27). Neutralizing mAbs against mouse PD-1 (RMPI-14) and PD-L2 (TY25) were kindly provided by Dr. H. Yagita, and a neutralizing mAb against mouse PD-L1 (MIH6) was kindly provided by Dr. M. Azuma.…”

“…1D, 1E) showed that Th17/Th1 cell expansion was detected during chronic GVHD and contributed to chronic GVHD progression (27). We next assessed Th subsets from pLNs of WT and PD-L1 2/2 recipients.…”