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Relapses occurring in most patients with lymphoma after antibody or chemotherapy highlight a need for effective vaccination approaches. Autologous tumors are ideal sources of patient-specific tumor antigens for vaccines; however, their poor immunogenicity has been a major obstacle in practice. Natural killer T (NKT) cells have recently emerged as crucial regulators of autoimmunity and tumor immunosurveillance. Here, we show that an autologous lymphoma vaccine that activates NKT cells generated t

Although resting B cells are known for being poorly immunogenic and for inducing T-cell tolerance, we have here attempted to test whether their immunogenicity could be enhanced by CD1d-restricted invariant T cells (iNKT) to a point where they could be used in cellular vaccines. We found that the addition of the iNKT ligand alpha-galactosylceramide (alphaGalCer) to peptide-loaded B cells overcame peptide-specific T-cell unresponsiveness and allowed for the generation of peptide-specific memory CT

Despite the clinically proven efficacies of immune checkpoint blockades, including anti-cytotoxic T lymphocyte-associated protein 4 antibody (αCTLA-4), the low response rate and immune-related adverse events (irAEs) in cancer patients represent major drawbacks of the therapy. These drawbacks of αCTLA-4 therapy are mainly due to the suboptimal activation of tumor-specific cytotoxic T lymphocytes (CTLs) and the systemic nonspecific activation of T cells. To overcome such drawbacks, αCTLA-4 is deli

Cross-presentation is a critical process by which antigen is displayed to CD8 T cells to induce tolerance. It is believed that CD8alpha+ dendritic cells (DCs) are responsible for cross-presentation, suggesting that the CD8alpha+ DC population is capable of inducing both cross-priming and cross-tolerance to antigen. We found that cross-tolerance against intestinal soluble antigen was abrogated in C57BL/6 mice lacking mesenteric lymph nodes (MLNs) and Peyer patches (PPs), whereas mice lacking PPs

NKT cells play contradictory roles in vivo, both regulating autoimmunity and activating immunity to intracellular pathogens and tumors. In this study, we studied the effect of NKT cell activation on the induction of systemic tolerance by oral administration of antigen. Administration of alpha-galactosylceramide (alphaGC) at the time of oral ovalbumin (OVA) feeding completely blocked the OVA-specific tolerance induced by both high- and low-dose regimens in BALB/c mice. In the mesenteric lymph nod

IL-17-producing cells promote terminal exhaustion of CD8⁺ T cells and tumor progression <i>in vivo</i>, which can be reversed by blockade of IL-17 or RORγt pathway. These findings unveil a novel role for IL-17-producing cells as tumor-promoting cells facilitating CD8⁺ T cell exhaustion, and propose type 17 immunity as a promising target for cancer immunotherapy.

Oral administration of soluble Ag before immunization induces peripheral tolerance and is effective in suppressing animal models of autoimmune diseases. Although tolerance induction in primed animals is more clinically relevant, it is not well studied. Therefore, this study was designed to examine the feeding effects on different phases of the immune response. We observed that feeding a single high dose (250 mg) of OVA to OVA-primed BALB/c mice could induce OVA-specific suppression in the Ab pro

BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis, offering a useful animal model to study autoimmune lupus. Although initial studies showed a critical contribution of IL-17 and Th17 cells in mediating autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh) cells remains incompletely understood. We found that both the frequency of Th17 cells and the levels of IL-17 in circulation in BXD2 mice were comparable to those of wild-type. By contras

CD1d-restricted Valpha14(+) invariant NK T (iNKT) cells are a specialized alphabeta T cell subset that regulates both innate and adaptive immunity. Although costimulatory molecules are required for the activation of conventional T cells and for the development of Foxp3(+) T cells, their role in iNKT cell regulation is unclear. Here we report that mice deficient in CD80/CD86 and/or B7h exhibit severe defects in thymic iNKT cell maturation, associated with largely reduced iNKT cell number in the t

CD4(+)CD25(+) regulatory T cells are thought to be generated in the periphery as well as in the thymus. We sought to determine the roles played by CD4(+)CD25(+) T cells and transforming growth factor-beta (TGF-beta) in the induction and maintenance of tolerance generated by oral antigens in BALB/c mice. We found that oral administration of a high dose of ovalbumin (OVA) suppressed OVA-specific proliferation and antibody production in BALB/c mice depleted of CD25(+) cells. In contrast, the unresp

Dendritic cells play an essential role in bridging innate and adaptive immunity by recognizing cellular stress including pathogen- and damage-associated molecular patterns and by shaping the types of antigen-specific T cell immunity. Although lidocaine is widely used in clinical settings that trigger cellular stress, it remains unclear whether such treatment impacts the activation of innate immune cells and subsequent differentiation of T cells. Here we showed that lidocaine inhibited the produc