T cells play a central role in the initiation and regulation of the immune response to foreign antigens. Full activation of T cells requires the engagement of T cell receptor complex (TCR) and the binding of a second costimulatory receptor to its ligand expressed on antigen presenting cells (APC). Among the molecules known to provide costimulatory function, CD28 has been the most dominant and potent costimulatory molecule. However, the function of CD28 is becoming more complex due to the recent discovery of its structural homologue, CTLA-4 and ICOS. This review summarizes the biology and physiologic function of each of these receptors, and further focuses on the biochemical mechanism underlying the function of these receptors. Complete understanding of the CD28/CTLA-4/ICOS costimulatory pathway will provide the basis for developing new therapeutic approaches for immunological dieseases.
Antigen-Presenting Cells ; Biology ; Receptors, Antigen, T-Cell ; T-Lymphocytes

We investigated whether diclofenac could influence the development of antigen-presenting cells in an oxygenated cholesterol-rich environment by determining its effects on the 27-hydroxycholesterol (27OHChol)-induced differentiation of monocytic cells into mature dendritic cells (mDCs). Treatment of human THP-1 monocytic cells with diclofenac antagonized the effects of 27OHChol by attenuating dendrite formation and cell attachment and promoting endocytic function. Diclofenac inhibited the transcription and surface expression of the mDC markers of CD80, CD83, and CD88, and reduced the 27OHChol-induced elevation of surface levels of MHC class I and II molecules to the basal levels in a dose-dependent manner. It also reduced the expression of CD197, a molecule involved in DC homing and migration. These results indicate that diclofenac inhibits the differentiation of monocytic cells into mDCs, thereby potentially modulating adaptive immune responses in a milieu rich in cholesterol oxidation products.
Antigen-Presenting Cells ; Cholesterol ; Dendrites ; Dendritic Cells* ; Diclofenac* ; Humans ; Oxygen

A mysterious puzzle in immunology is how the immune system decides what types of immune response to initiate against various stimuli. Although much is known about control of T helper 1 (Th1) and Th17 responses, the mechanisms that initiate Th2 responses remain obscure. Antigen-presenting cells, particularly dendritic cells (DCs), are mandatory for the induction of a Th cell response. Numerous studies have documented the organizing role of DCs in this process. The present review summarizes the fundamental roles of DCs in inducing Th2 responses.
Allergy and Immunology ; Antigen-Presenting Cells ; Dendritic Cells* ; Immune System

Dendritic cells (DCs) are professional antigen-presenting cells capable of initiating and regulating innate and adaptive immunity. The development of effective ways to produce a large number of DCs in laboratories made the use of DCs available in various vaccine approaches. Compared to conventional vaccines, focused on protective antibody responses, DC vaccines emphasize protective T cell immunity but might elicit strong antibody responses as well. In addition, the recent discoveries of functionally distinct DC subsets in various organs and tissues are likely to increase the potential of exploiting DCs in vaccines and immunotherapy. Vaccines composed of DCs generated ex vivo, pulsed with antigens, and matured prior to being re-infused to the body have been widely tried clinically but resulted in limited success due to various obstacles. In this review, new approaches that protein vaccines are selectively targeted to the endocytic C-type lectin receptors on surface of DCs in vivo are discussed.
Adaptive Immunity ; Antibody Formation ; Antigen-Presenting Cells ; Dendritic Cells* ; Immunotherapy ; Lectins, C-Type* ; Receptors, Antigen ; Vaccines

Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.
Animals ; Antigen Presentation* ; Antigen-Presenting Cells ; Immune System ; Immunotherapy ; Metformin* ; Mice ; Ovum

Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.
Antigen-Presenting Cells ; Autoimmune Diseases ; Humans ; Ligands ; Membrane Glycoproteins ; Receptors, Antigen, T-Cell ; T-Lymphocytes

CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although alpha-galactosylceramide (alpha-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-gamma by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.
Antigen-Presenting Cells ; B-Lymphocytes* ; Coculture Techniques ; Dendritic Cells ; Galactosylceramides ; Interleukin-4 ; Natural Killer T-Cells*

Dendritic cells (DCs) are crucial in the defense against pathogens and allergen. The ability of allergens to cause allergic inflammation is contingent upon the presence of microenvironment that either privileges Th2 responses or prohibits these reactions. As a simplification, this review tried to prove a causal relationship between a allergic disease and dendritic cell by satisfying the modified Koch's postulates. DCs express C-type lectin receptors (CLRs) and Toll like receptors (TLRs). DCs take up almost all allergen through CLRs. Uptake of allergen by CLRs leads to the production of anti-inflammatory reactions. Although both TLRs and CLRs have distinct functions, the balance between both receptors is instrumental for the immunological outcome.
Allergens ; Antigen-Presenting Cells ; Dendritic Cells* ; Inflammation ; Lectins, C-Type ; Toll-Like Receptors

Dendritic cells (DCs) are potent antigen-presenting cells and generated from diverse sources including monocytes which are known to be the sites for human cytomegalovirus (HCMV) latency. HCMV has been known to suppress or evade from immune functions involving monocytes and DC. Thus, it was attempted to investigate the effect of HCMV infection on the differentiation of DCs from monocytes. Monocytes were prepared from peripheral blood mononuclear cells and they expressed high levels of CD14, CD11a, CD11b, CD11c and HLA molecules, while they did not express lymphocyte-specific CD molecules. The surface expressions of CD molecules and HLA in immature DCs (imDCs) differentiated from HCMV-infected monocytes differed from those in uninfected imDCs. Specifically, the expressions of CD11a, CD11b, CD11c, CD40 and HLA-DR were decreased compared to uninfected imDCs, while CD80 expression was increased in imDCs differentiated from HCMV-infected monocytes. DCs were allowed to mature (mDCs) by treating imDCs with interferon gamma and LPS. When HCMV-infected imDCs were differentiated to mDCs, the expression of mDC-specific CD83 as well as HLA molecules were decreased. Thus, our results suggest that HCMV inhibits phenotytpic differentiation of DCs.
Antigen-Presenting Cells ; Cytomegalovirus* ; Dendritic Cells* ; HLA-DR Antigens ; Humans* ; Interferons ; Monocytes

Dendritic cells (DCs) are the most professional antigen presenting cells that play important roles in connection between innate and adaptive immune responses. Numerous studies revealed that the functions of DCs are related with the capture and processing of antigen as well as the migration to lymphoid tissues for the presenting antigens to T cells. These unique features of DCs allow them to be considered as therapeutic vaccines that can induce immune responses and anti-tumor activity. Here, we discuss and understand the immunological basis of DCs and presume the possibilities of DC-based vaccines for the promising cancer therapy.
Antigen-Presenting Cells ; Cancer Vaccines ; Dendritic Cells ; Immunotherapy ; Lymphoid Tissue ; T-Lymphocytes ; Vaccines