Collectively, our results suggest that VSIG4(+) KCs play a critical role in the induction and maintenance of liver T- and NKT-cell tolerance, and that modulation of the VSIG4 pathway using a VSIG4.Ig fusion protein may provide useful immunological therapies against immune-mediated liver injury including autoimmune hepatitis.

The physiologic function of natural killer T (NKT) cells in adaptive immunity remains largely unknown because most studies have used NKT cell agonists. In the present study, the role of NKT cells during the secondary effector phase was investigated separately from the primary immunization phase via adoptive transfer of differentiated effector T cells into naive recipients. We found that secondary antitumor CD8(+) T-cell responses were optimal when NKT cells were present. Tumor-specific CD8(+) effector T cells responded less strongly to tumor cell challenge in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT cell-mediated enhancement of the secondary antitumor CD8(+) T-cell response was concurrent with increased number and activity of tumor-specific CD8(+) T cells. These findings provide the first demonstration of a direct role for NKT cells in the regulation of antigen-specific secondary T-cell responses without the use of exogenous NKT cell agonists such as alpha-galactosylceramide (alpha-GalCer). Furthermore, forced activation of NKT cells with alpha-GalCer during the secondary immune response in suboptimally immunized animals enhanced otherwise poor tumor rejection responses. Taken together, our findings strongly emphasize the importance of NKT cells in secondary CD8(+) T-cell immune responses.

NK1 T cells are a specialized population of alpha/beta T cells that coexpress receptors of the NK lineage and have the unique potential to very rapidly secrete large amounts of cytokines, providing early help for effector cells and regulating the Th1 or Th2 differentiation of some immune responses. NK1 T cells express a restricted TCR repertoire made of an invariant TCR alpha chain, V alpha 14-J alpha 281, associated with polyclonal V beta 8, V beta 7, and V beta 2 TCR beta chains. NK1 T cells recognize the products of the conserved family of MHC class I-like CD1 genes, apparently in the absence of foreign antigens. Thus, this novel regulatory pathway, which straddles the innate and the adaptive immune systems, is unique in that its activation may not require associative recognition of antigen. Here, we review the specificity and function of mouse NK1 T cells, and we discuss the relationship of this lineage to mainstream T cells and NK cells.

Tricin, a flavone belonging to the Gramineae family, has been confirmed to be the primary compound in a Zizania latifolia extract (ZLE) that prevents allergies.Various allergic reactions occur because of the unbalanced differentiation of T help cells (Th) and the consequent overproduction of IgE.Therefore, the regulation of Th1 and Th2 responses by T helper cell differentiation is essential for suppressing allergic responses.This study confirmed the immunomodulatory effects of ZLE and the major compound tricin in an OVA-sensitized mouse model.The IgE and OVA-specific production of tricin and ZLE in plasma were investigated in OVA-sensitized mice.The effects of www.videleaf.comtricin and ZLE on the amount of Th1 and Th2 cytokines and transcription factors released in splenocytes were investigated in OVA-sensitized mice.The skin roughness and the number of mast cells were confirmed by staining the skin surface with H&E and toluidine blue.Tricin and ZLE reduced the plasma IgE and OVA-specific-IgE levels significantly compared to the OVA group.On the other hand, tricin and ZLE promoted the release of the Th1 cytokines IL-12 and IFN- and inhibited the release of Th2 cytokines in OVA-sensitized mice.Tricin and ZLE induced T-bet and NFATc2 expression, anddown regulated GATA-3 levels.The skin roughness and the number of mast cells decreased in the OVA-immunized mice.Overall, the data indicate that tricin and ZLE may prevent allergy-related diseases through immunomodulation.

Bone marrow stromal antigen 2 (BST2) is a host-restriction factor that plays multiple roles in the antiviral defense of innate immune responses, including the inhibition of viral particle release from virus-infected cells. BST2 may also be involved in the endothelial adhesion and migration of monocytes, but its importance in the immune system is still unclear. Immune cell adhesion and migration are closely related to the initiation of immune responses. In this study, we found that the expressions of the lymph node homing marker chemokine receptor 7 (CCR7) and an adhesion molecule intercellular adhesion molecule 1 (ICAM-1) in conventional dendritic cells (cDCs) were associated with BST2 expression. Interestingly, <i>Bst2</i>^-/- cDCs showed lower chemotactic ability, including velocity and accumulative distance toward chemokine ligand 19 (CCL19) gradient in vitro, compared to wild-type cDCs. <i>Bst2</i>^-/- cDCs also showed reduced migration and reduced retention capacity in draining lymph nodes in vivo. As a result, <i>Bst2</i>^-/- cDCs as antigen-presenting cells induced lower antigen-specific B cell and T cell responses compared to <i>Bst2</i>^+/+ cDCs. Notably, mice administered the influenza vaccine via <i>Bst2</i>^-/- cDCs exhibited substantially inefficient virus clearance compared to mice administered the <i>Bst2</i>^+/+ cDCs vaccine. Therefore, we propose that BST2, which plays a critical role in the effective migration and retention of cDCs, is involved in the development of optimal immunological effects in draining lymph nodes.

Invariant natural killer T (iNKT) cells are involved in various autoimmune diseases. Although iNKT cells are arthritogenic, transforming growth factor beta (TGFβ)-treated tolerogenic peritoneal macrophages (Tol-pMφ) from wild-type (WT) mice are more tolerogenic than those from CD1d knock-out iNKT cell-deficient mice in a collagen-induced arthritis (CIA) model. The underlying mechanism by which pMφ can act as tolerogenic antigen presenting cells (APCs) is currently unclear. To determine cellular mechanisms underlying CD1d-dependent tolerogenicity of pMφ, in vitro and in vivo characteristics of pMφ were investigated. Unlike dendritic cells or splenic Mφ, pMφ from CD1d+/- mice showed lower expression levels of costimulatory molecule CD86 and produced lower amounts of inflammatory cytokines upon lipopolysaccharide (LPS) stimulation compared to pMφ from CD1d-deficient mice. In a CIA model of CD1d-deficient mice, adoptively transferred pMφ from WT mice reduced the severity of arthritis. However, pMφ from CD1d-deficient mice were unable to reduce the severity of arthritis. Hence, the tolerogenicity of pMφ is a cell-intrinsic property that is probably conferred by iNKT cells during pMφ development rather than by interactions of pMφ with iNKT cells during antigen presentation to cognate T cells. [BMB Reports 2021; 54(4): 209-214].

Collectively, our results suggest that VSIG4(+) KCs play a critical role in the induction and maintenance of liver T- and NKT-cell tolerance, and that modulation of the VSIG4 pathway using a VSIG4.Ig fusion protein may provide useful immunological therapies against immune-mediated liver injury including autoimmune hepatitis.

The physiologic function of natural killer T (NKT) cells in adaptive immunity remains largely unknown because most studies have used NKT cell agonists. In the present study, the role of NKT cells during the secondary effector phase was investigated separately from the primary immunization phase via adoptive transfer of differentiated effector T cells into naive recipients. We found that secondary antitumor CD8(+) T-cell responses were optimal when NKT cells were present. Tumor-specific CD8(+) effector T cells responded less strongly to tumor cell challenge in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT cell-mediated enhancement of the secondary antitumor CD8(+) T-cell response was concurrent with increased number and activity of tumor-specific CD8(+) T cells. These findings provide the first demonstration of a direct role for NKT cells in the regulation of antigen-specific secondary T-cell responses without the use of exogenous NKT cell agonists such as alpha-galactosylceramide (alpha-GalCer). Furthermore, forced activation of NKT cells with alpha-GalCer during the secondary immune response in suboptimally immunized animals enhanced otherwise poor tumor rejection responses. Taken together, our findings strongly emphasize the importance of NKT cells in secondary CD8(+) T-cell immune responses.