ABSTRACT
Implantation of an embryo occurs during the mid-secretory phase of the menstrual cycle, known as the "implantation window." During this implantation period, there are significant morphologic and functional changes in the endometrium, which is followed by decidualization. Many immune cells, such as dendritic and natural killer (NK) cells, increase in number in this period and early pregnancy. Recent works have revealed that antigen-presenting cells (APCs) and NK cells are involved in vascular remodeling of spiral arteries in the decidua and lack of APCs leads to failure of pregnancy. Paternal and fetal antigens may play a role in the induction of immune tolerance during pregnancy. A balance between effectors (i.e., innate immunity and helper T [Th] 1 and Th17 immunity) and regulators (Th2 cells, regulatory T cells, etc.) is essential for establishment and maintenance of pregnancy. The highly complicated endocrine-immune network works in decidualization of the endometrium and at the fetomaternal interface. We will discuss the role of immune cells in the implantation period and during early pregnancy.
Subject(s)
Female , Humans , Pregnancy , Antigen-Presenting Cells , Arteries , Decidua , Dendritic Cells , Embryonic Structures , Endometrium , Immune Tolerance , Immunity, Innate , Killer Cells, Natural , Lymphocytes , Macrophages , Menstrual Cycle , T-Lymphocytes, Regulatory , Th17 CellsABSTRACT
Due to their high immunostimulatory ability as well as the critical role they play in the maintenance of self-tolerance, dendritic cells have been implicated in the pathogenesis of autoimmune diseases. The non-obese diabetic (NOD) mouse is an animal model of autoimmune type 1 diabetes, in which pancreatic beta cells are selectively destroyed mainly by T cell-mediated immune responses. To elucidate initiation mechanisms of beta cell-specific autoimmunity, we attempted to generate bone marrow-derived dendritic cells from NOD mice. However, our results showed low proliferative response of NOD bone marrow cells and some defects in the differentiation into the myeloid dendritic cells. NOD dendritic cells showed lower expressions of MHC class II, B7-1, B7-2 and CD40, compared with C57BL/6 dendritic cells. In mixed lymphocyte reactions, stimulatory activities of NOD dendritic cells were also weak. Treatment with LPS, INF-gamma and anti-CD40 stimulated NOD dendritic cells to produce IL-12p70. The amount of IL-12, however, appeared to be lower than that of C57BL/6. Results of the present study indicated that there may be some defects in the development of NOD dendritic cells in the bone marrow, which might have an impact on the breakdown of self tolerance.
Subject(s)
Mice , Animals , Autoimmune Diseases/pathology , Autoimmune Diseases/immunology , Bone Marrow Cells/pathology , Bone Marrow Cells/immunology , Bone Marrow Cells/chemistry , Cell Differentiation/immunology , Cell Differentiation/drug effects , Dendritic Cells/pathology , Dendritic Cells/immunology , Dendritic Cells/chemistry , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/immunology , Enzyme-Linked Immunosorbent Assay , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Interleukin-12/analysis , Interleukin-4/pharmacology , Lipopolysaccharides/pharmacology , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred NOD , ObesityABSTRACT
The cytokine pattern on viral antigen recognition is believed to exert a profound influence on the resolution of viral infections and viral clearance. This study was initiated to investigate whether a cytokine imbalance oriented toward Th2 type response plays a role in chronic hepatitis B. Cytokine profiles of peripheral blood mononuclear cells associated with chronic hepatitis B were analysed by RT-PCR. Upon HBsAg stimulation, expression of IFN-gamma, IL-2, IL-4, and IL-10 was detected in 41%, 8%, 41%, and 50% of the patients, respectively. Among these cytokines, the expression of IFN-gamma was associated with high levels of serum AST/ALT. However, we could not prove that Th2 type cytokines had a protective effect on hepatocytes. Upon HBxAg stimulation, there was no recognizable association of cytokine patterns with AST/ALT levels. In conclusion, production of a Th1 cytokine, IFN-gamma, by HBsAg-reactive cells was associated with hepatocyte damage in chronic hepatitis B, while no counteracting effect of Th2 cytokines produced by those cells was observed.
Subject(s)
Humans , Cytokines/genetics , Cytokines/biosynthesis , Hepatitis B Surface Antigens/pharmacology , Hepatitis B Surface Antigens/immunology , Hepatitis B, Chronic/immunology , Interferon-gamma/genetics , Interferon-gamma/biosynthesis , Leukocytes, Mononuclear/immunology , Liver/cytology , Recombinant Fusion Proteins/pharmacology , Recombinant Fusion Proteins/immunology , Th1 Cells/immunology , Th1 Cells/drug effects , Th2 Cells/immunology , Th2 Cells/drug effects , Trans-Activators/pharmacology , Trans-Activators/immunologyABSTRACT
The T cell responses to hepatitis B surface antigen (HBsAg) were analyzed in acute hepatitis patients, chronic active hepatitis (CAH) patients and asymptomatic carriers. Neither proliferative responses nor substantial cytokine production of peripheral blood mononuclear cells (PBMC) in response to HBsAg was detected. For further studies, HBsAg- reactive T cell lines were prepared from PBMC of the hepatitis patients and asymptomatic carriers. No proliferative response of the T cell lines was observed. Interestingly, however, T cell lines obtained from acute hepatitis patients were found to produce IFN-r, but not IL- 4, in response to HBsAg stimulation, whereas T cell lines obtained from CAH patients and carriers were not. Results of this study suggest that HBsAg-reactive T cells producing Thl type cytokines may play an important role in the viral clearance during acute infections, while defects in those T cells may be responsible for the viral persistency.
Subject(s)
Humans , Cell Line , Cytokines , Hepatitis , Hepatitis B Surface Antigens , Hepatitis, Chronic , T-LymphocytesABSTRACT
No abstract available.
Subject(s)
Antibodies , Enzyme-Linked Immunosorbent Assay , Orientia tsutsugamushi , RickettsiaABSTRACT
A new photosensitizer, CpD(chlorophyll derivatives), previously reported as a promising agent for tumor therapy, was studied to determine its inhibitory effects on Gross leukemia virus(GLV), a mouse retrovirus isolated from the GLV-producing TGV cell line, and the cytocidal effect on the GLV infected cells in vitro, following photodynamic treatment with CpD-D and red light, the viral inactivation and infectivity were examined by measuring the reverse transcriptase(RT) activity of the virus itself and that in cell-free culture supernatant of freshly GLV-infected secondary mouse embryo cells respectively. The cytocidal activity was measured by trypan blue exclusion test. Inhibition of GLV associated RT activity resulted from CpD-D and red light treatment. The RT inhibition effect was immediate and the infectivity of these photodynamically treated GLV to mouse embryo cells was also inhibited. However, specific cytotoxicity of GLV infected cells was not found. Thus, it is concluded that CpD-D may be used as an effective antiviral agent.