Autophagy is a specialized cellular pathway involved in maintaining homeostasis by degrading long-lived cellular proteins and organelles. Recent studies have demonstrated that autophagy is utilized by immune systems to protect host cells from invading pathogens and regulate uncontrolled immune responses. During pathogen recognition, induction of autophagy by pattern recognition receptors leads to the promotion or inhibition of consequent signaling pathways. Furthermore, autophagy plays a role in the delivery of pathogen signatures in order to promote the recognition thereof by pattern recognition receptors. In addition to innate recognition, autophagy has been shown to facilitate MHC class II presentation of intracellular antigens to activate CD4 T cells. In this review, we describe the roles of autophagy in innate recognition of pathogens and adaptive immunity, such as antigen presentation, as well as the clinical relevance of autophagy in the treatment of human diseases.
Adaptive Immunity/immunology/*physiology ; Animals ; Antigen Presentation/immunology/physiology ; Autophagy/immunology/*physiology ; Humans ; Major Histocompatibility Complex/immunology/physiology

DNA vaccination that can induce both cellular and humoral immune response has become an attractive immunization strategy against cancer and infectious disease. Elucidation of the precise mechanisms of immune priming will be important in the development of effective DNA vaccines. In this review, we illustrate possible mechanisms in priming cytotoxic T cell response involving the intracellular degradation, processing and presentation of encoded antigen. We also discuss the roles of costimulatory molecules expressed on antigen-presenting cells (APCs) in inducing optimal CTL activity. Hence, a rational strategy for increasing DNA potency would be to facilitate these pathways. Additionally, we focus on recent strategies including rapid degradation of ubiquitin-antigen fusion proteins, direct targeting to APCs for increased DNA uptake, direct routing an antigen into the MHC class I and II processing and presentation pathways, and increasing the immunogenicity of encoded antigen. All of these approaches have resulted in increased potency of DNA vaccines.
Animals ; Antigen Presentation ; Antigen-Presenting Cells ; immunology ; Lysosomes ; immunology ; Mice ; T-Lymphocytes, Cytotoxic ; immunology ; Ubiquitin ; physiology ; Vaccines, DNA ; genetics ; immunology

OBJECTIVETo study the role of dendritic cells (DCs) and macrophages, differentiated from the same individual peripheral blood monocytes, in tumor antigen- presenting.

METHODSDCs and macrophages were differentiated from human peripheral blood monocytes by adding both Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) or GM-CSF only. Then they were loaded with tumor antigen at different concentrations and cocultured with autologous T cells in 96-well flat-bottomed microtiter plates for five days at 37 degrees C, 5% CO(2). (3)H-thymine was added before the culture terminated, and twelve hours later, the cells were gathered to test the cpm value.

RESULTSBoth DCs and macrophages chased with tumor antigen could strongly stimulate the proliferation of autologous T cells, especially DCs. The stimulation effect with 20 microl/ml antigen was the most remarkable and the cmp values were 11,950.3 +/-1621.8, 8,708.5 +/-176.1, 402.5+/-43.1 in DCs group, Macrophages group, and lymphocytes group, respectively.

CONCLUSIONThe antigen presenting role of DCs is stronger than that of macrophages from the same individual.

Antigen Presentation ; immunology ; Antigen-Presenting Cells ; immunology ; physiology ; Antigens, Neoplasm ; immunology ; Carcinoma, Hepatocellular ; immunology ; Dendritic Cells ; immunology ; physiology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Liver Neoplasms ; immunology ; Macrophages ; immunology ; physiology ; Tumor Cells, Cultured

BACKGROUNDAntigen-loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2-type cytokine production in the draining lymph nodes. The aim of the present study was to evaluate whether EOSs within the tracheobronchial lumen can stimulate Th2 cell expansion in the lung tissues.

METHODSAirway EOSs were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these EOSs were then cocultured with CD4+ cells isolated from sensitized mice in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway EOSs were instilled into the trachea of sensitized mice. At the day 3 thereafter, the lung tissues were removed and prepared into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines.

RESULTSAirway EOSs functioned as CD80- and CD86-dependent antigen-presenting cells to stimulate lung CD4+ lymphocytes to produce interleukin-4, interleukin-5 and interleukin-13, but not interferon-gamma in in vitro assay. When instilled intratracheally in sensitized recipient mice, airway EOSs primed lung Th2 cells in vivo for interleukin-4, interleukin-5 and interleukin-13, but not interferon-gamma, production during the in vitro culture that was also CD80- and CD86-dependent.

CONCLUSIONEOSs within the lumina of airways could process inhaled antigen and function in vitro and in vivo as antigen-presenting cells to promote expansion of Th2 cells in the lungs.

Animals ; Antigen Presentation ; Antigens, CD ; physiology ; B7-1 Antigen ; physiology ; B7-2 Antigen ; Cytokines ; biosynthesis ; Eosinophils ; physiology ; Female ; Lung ; immunology ; Membrane Glycoproteins ; physiology ; Mice ; Mice, Inbred BALB C ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVETo explore the role of indirect antigen presentation pathway on the immunogenecity of epidermal cells.

METHODSHuman epidermal cells (HEC), allogeneic human peripheral blood lymphocytes (PBL) and mononuclear cells (PBM, including monocytes) were isolated and cultured in vitro. HECs were transfected by human-originated CTLA4Ig-adenovirus vector. The CTLA4Ig expression was observed. Allogeneic PBLs or PBMs were added to the transfected and non-transfected HECs with simple cultured PBLs and PBMs as the control. The proliferation of PBL and PBM was determined by (3)H-TdR incooperation.

RESULTSHECs could be successfully transfected by CTLA4Ig-adenovirus vector and expressed corresponding proteins. The non-transfected HECs could stimulate slight proliferation of allogeneic PBLs (P < 0.05) and stimulate remarkable proliferation of PBMs (including monocytes) (P < 0.05). The proliferation reaction of PBLs and PBMs decreased significantly (P < 0.05) after being stimulated by HEC which was modulated by CTLA4Ig genes.

CONCLUSIONIndirect antigen presentation pathway might play important roles in the HEC immunogenicity which could be evidently inhibited by CTLA4Ig.

Adenoviridae ; genetics ; Antigen Presentation ; immunology ; physiology ; Antigens, CD ; Antigens, Differentiation ; genetics ; immunology ; CTLA-4 Antigen ; Cell Division ; immunology ; Cells, Cultured ; Coculture Techniques ; Epidermis ; cytology ; immunology ; metabolism ; Genetic Vectors ; genetics ; Humans ; Leukocytes, Mononuclear ; cytology ; immunology ; Lymphocytes ; cytology ; immunology ; Signal Transduction ; Transfection

Dendritic cells (DCs) as a rare type of leukocytes play an important role in bridging the innate and adaptive immune system. A subset of DCs, monocyte-derived dendritic cells (moDCs), exists in very low numbers at steady state but become abundant in inflammatory states. These inflammation-associated DCs are potent producers of pro-inflammatory cytokines and potent inducers of T helper differentiation. They behave as a "double-edge" sword so that they not only mediate protective immunity but also immuno-pathology. It is still incompletely understood how their function is regulated. Emerging evidence indicates that microRNAs (miRNAs), as a new class of gene regulators, potently regulate the function of moDCs. Here we summarize recent progress in this area.
Animals ; Antigen Presentation ; genetics ; Cell Differentiation ; Cytokines ; genetics ; metabolism ; Dendritic Cells ; metabolism ; physiology ; Humans ; Inflammation ; immunology ; pathology ; MicroRNAs ; metabolism ; physiology ; RNA Interference

Neutrophils are also known to acquire the characteristics of dendritic cells (DCs) under the appropriate conditions. In this study, neutrophils were cultivated in vitro in the presence or absence of compounds modulating their survival in an attempt to characterize the expression profile of the DC markers. Higher MHC-II, CD80, CD86, CD83, and CD40 expression levels were detected on the surface of the cultured neutrophils for 24 h than on the freshly isolated cells. The annexin V-positive cells showed a higher expression level of the DC markers than the annexin V-negative cells. The population of neutrophils double stained with annexin V and the DC markers increased after being incubated with agonistic anti-Fas Ab. LPS, the anti-apoptotic compound, decreased the CD86 and MHC-II expression levels but 50-60% of the DC marker-positive cells were detected in the annexin V-positive cells. In contrast, CD80, CD86, CD83, and HLA-DR mRNA levels increased in the GM-CSF-treated neutrophils but not in the anti-Fas Ab-treated neutrophils. T cell proliferation was inhibited by co-culturing them with anti-Fas Ab- or LPS-treated neutrophils at a high neutrophil:T cell ratio. However, the superantigen-mediated T cell proliferation was increased by the LPS-treated neutrophils but decreased by the anti-Fas Ab-treated neutrophils. There was a lower level of interferon-gamma production in the T cells co-cultured with anti-Fas Ab-treated neutrophils than with the LPS-treated neutrophils. This suggests that apoptotic neutrophils express DC markers on their surface and the differential expression of DC markers might have a detrimental effect on the immune reaction.
Antigen Presentation ; Antigens, CD/biosynthesis ; Antigens, CD95/pharmacology ; Antigens, Differentiation/*biosynthesis ; *Apoptosis ; Cells, Cultured ; Dendritic Cells/*metabolism ; Humans ; Lipopolysaccharides/pharmacology ; Lymphocyte Activation ; Neutrophils/*metabolism/physiology ; T-Lymphocytes/immunology

OBJECTIVETo define roles of B7-1 co-stimulation factor expressed in human malignant cell lines in mediating anti-tumor T cell immune responses.

METHODSExamining human leucocyte antigen (HLA) and B7 expressions on 8 human blood malignancies cell lines by flow cytometry. Transfecting B7-1 gene to B7-1 negative (B7(-)) Raji and B7(-) Jurkat cell lines by liposome, and comparing the potencies of blood malignant cell lines in the induction of T cell activation by examination of T cell cytokine mRNAs before and after transfection using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).

RESULTSHigh level of HLA I and II molecules were expressed in most human blood malignant cell lines examined, and the co-stimulatory factor B7-2 was also highly expressed. In contrast, another member of B7 family: B7-1 was either not expressed or very limitedly expressed in most of these hematopoietic malignant cell lines. Most importantly, transfection of B7-1 gene to B7(-). Raji and B7(-). Jurkat cell lines made these cell lines better antigen presenting cells for stimulation of anti-tumor T cell activation, which was demonstrated by up regulation of expression of T cell cytokines IL-2, IL-4 and INF-gamma mRNAs after incubation of these tumor cells with T cells for 24 h.

CONCLUSIONSB7 co-stimulation plays an important role in anti-tumor immunity. Transfection of B7-1 gene to the human hematopoietic malignant cell lines that are deficient in the B7-1 expression empowers their antigen presentation potency for activation of anti-tumor T cells. Our results suggested that repairing the deficiency of B7-1 co-stimulatory pathway in tumor cells might be a novel immunotherapeutic approach for human hematopoietic malignancies.

Antigen Presentation ; Antigens, CD ; analysis ; B7-1 Antigen ; analysis ; physiology ; B7-2 Antigen ; Cytokines ; genetics ; Flow Cytometry ; HLA-DR7 Antigen ; physiology ; Hematologic Neoplasms ; immunology ; Humans ; K562 Cells ; Lymphocyte Activation ; Membrane Glycoproteins ; analysis ; RNA, Messenger ; analysis ; T-Lymphocytes ; immunology ; Transfection ; U937 Cells