Aplastic anemia(AA) is mostly considered as an immune-mediated bone marrow failure syndrome, characterized by pancytopenia and bone marrow hypoplasia. The pathogenesis of AA is complicated, until now it is not fully understood. Further study on the pathological mechanism will be helpful for the diagnosis and treatment of AA. CD8(+) T cells and their secreted cytokines play important roles in the abnormal immunity during the process of AA. Thus, this review focuses on the role of CD8(+) T cells and their secreted cytokines in the pathogenesis of AA.
Anemia, Aplastic ; immunology ; metabolism ; pathology ; CD8-Positive T-Lymphocytes ; immunology ; metabolism ; secretion ; Cytokines ; metabolism ; Humans ; Immunity, Cellular

OBJECTIVEAntigen-presenting cells such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation during adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Tanshinone II A (TSN) had been shown to decrease the growth of atherosclerotic lesions. We therefore investigated the ability of TSN to inhibit human monocyte-derived DCs and their T-cellstimulatory capacity.

METHODSDCs derived from human monocytes cultured with recombinant human interleukin (IL)-4 and recombinant human granulocyte-macrophage colony-stimulating factor were co-cultured with TSN and lipopolysaccharide for 48 h. Phosphate-buffered saline was used as a negative control. Activation markers and the capacity of DCs for endocytosis were measured by flow cytometry, and proinflammatory cytokines were measured by enzyme-linked immunosorbent assays. DCs were co-cultured with lymphocytes to measure T-cell proliferation and IL-2 secretion by mixed lymphocyte reactions.

RESULTSTSN dose-dependently attenuated DC expression of costimulatory molecules (CD86), and decreased expression of major histocompatibility complex class II (human loukocyte antigen-DR) and adhesion molecules (CD54). Moreover, TSN reduced secretion of the proinflammatory cytokines IL-12 and IL-1 by human DCs, and restored the capacity for endocytosis. Finally, TSN-preincubated DCs showed a reduced capacity to stimulate T-cell proliferation and cytokine secretion.

CONCLUSIONSTSN inhibits DC maturation and decreases the expression of proinflammatory cytokines, while impairing their capacity to stimulate T-cell proliferation and cytokine secretion. These effects may contribute to the influence of TSN on the progression of atherosclerotic lesions.

Antigen-Presenting Cells ; drug effects ; Atherosclerosis ; immunology ; pathology ; B7-2 Antigen ; metabolism ; Cell Membrane ; drug effects ; metabolism ; Cytokines ; secretion ; Dendritic Cells ; drug effects ; immunology ; secretion ; Diterpenes, Abietane ; pharmacology ; Endocytosis ; drug effects ; Flow Cytometry ; Humans ; Immunity, Cellular ; drug effects ; Inflammation Mediators ; metabolism ; Lymphocyte Activation ; drug effects

Adult ; Antibodies, Monoclonal ; pharmacology ; Bronchoalveolar Lavage Fluid ; cytology ; Cells, Cultured ; Cytokines ; biosynthesis ; blood ; secretion ; Fas Ligand Protein ; antagonists & inhibitors ; metabolism ; Humans ; Macrophages, Alveolar ; immunology ; metabolism ; Middle Aged ; Occupational Exposure ; analysis ; Signal Transduction ; Silicon Dioxide ; adverse effects ; Silicosis ; blood ; immunology ; fas Receptor ; antagonists & inhibitors ; metabolism

BACKGROUNDA recent study demonstrated that the inflammatory response accompanying necrotic brain injury played an important role in stroke. Thus, inhibition of this response may help to stop the expansion of infarcts. It has been also shown that the spleen, a major peripheral immune organ, plays a role in stroke-induced immune responses. This study aimed to establish rat models of middle cerebral artery occlusion (MCAO) and to investigate the effect of splenectomy and possible mechanisms in that rat models.

METHODSInfarct size in a stroke model was measured with the Nissl body staining method, numbers of inflammatory cells in ischemic regions were detected by immunofluorescence staining, and inflammatory factors were assayed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR) in brain homogenates and sera. The significance of differences was determined by one-way analysis of variance (ANOVA) followed by the least significant difference post hoc test.

RESULTSInfarct size in the brain of rats that underwent splenectomies 2 weeks before permanent MCAO ((34.93 ± 3.23)%) was over 50% smaller than that of rats subjected to the stroke surgery alone ((74.33 ± 2.36)%, P < 0.001; (77.30 ± 2.62)%, P < 0.001). Lower numbers of T cells, neutrophils, and macrophages in brain tissue and lower levels of pro-inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, were observed in rats that underwent splenectomies, compared with the two other groups, but splenectomized rats showed higher levels of the anti-inflammatory factor IL-10 in the brain.

CONCLUSIONThe mechanism(s) by which splenectomy protects brain from damage induced by stroke may correlate with the decreased numbers of inflammatory cells and changes in inflammatory cytokines.

Animals ; Cerebral Infarction ; prevention & control ; Cytokines ; secretion ; Inflammation ; prevention & control ; Male ; Rats ; Rats, Sprague-Dawley ; Splenectomy ; Stroke ; complications ; T-Lymphocytes ; immunology

This study was aimed to evaluate the effect of lentinan on the immune function of splenic lymphocytes in rotary cell culture system (RCCS) microgravity environment. The splenic lymphocytes from mice were separated and cultured in the normal gravity and the microgravity environments. The cells were treated with lentinan solution (0, 10, 20 and 40 µg/ml). After incubated with lentinan for indicated times (24, 48 and 72 h), the cell proliferation, secretion of cytokine and the expression of cell surface markers were detected by MTT method, ELISA and flow cytometry respectively. The results indicated that lentinan of above mentioned concentrations did not obviously promote the lymphocyte proliferation, but increased the secretion of IL-2 and IFN-γ and enhanced the expression of lymphocyte surface markers CD4 and CD8 in microgravity environment. It is concluded that lentinan has the ability to enhance the lymphocyte immune function in microgravity environment.
Animals ; Cells, Cultured ; Cytokines ; secretion ; Immune Tolerance ; drug effects ; Immunosuppression ; Lentinan ; pharmacology ; Lymphocyte Activation ; drug effects ; immunology ; Lymphocytes ; cytology ; drug effects ; immunology ; Mice ; Mice, Inbred C57BL ; Spleen ; cytology ; Weightlessness Simulation

Cytokines ; metabolism ; Humans ; Leukocytes, Mononuclear ; immunology ; secretion ; Ubiquitin ; blood

This study investigated whether elevated host immune capacity can inhibit T. gondii infection. For this purpose, we used silk protein extracted from Bombyx mori cocoons as a natural supplement to augment immune capacity. After silk protein administration to BALB/c mice for 6 weeks, ratios of T lymphocytes (CD4+ and CD8+ T-cells) and splenocyte proliferative capacities in response to Con A or T. gondii lysate antigen (TLA) were increased. Of various cytokines, which regulate immune systems, Th1 cytokines, such as IFN-gamma, IL-2, and IL-12, were obviously increased in splenocyte primary cell cultures. Furthermore, the survival of T. gondii (RH strain)-infected mice increased from 2 days to 5 or more days. In a state of immunosuppression induced by methylprednisolone acetate, silk protein-administered mice were resistant to reduction in T-lymphocyte (CD4+ and CD8+ T-cells) numbers and the splenocyte proliferative capacity induced by Con A or TLA with a statistical significance. Taken together, our results suggest that silk protein augments immune capacity in mice and the increased cellular immunity by silk protein administration increases host protection against acute T. gondii infection.
Animals ; Bombyx/*chemistry ; CD4-CD8 Ratio ; Cell Proliferation ; Cells, Cultured ; Cytokines/secretion ; Insect Proteins/*immunology ; Leukocytes, Mononuclear/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Silk/immunology ; Spleen/immunology ; Survival Analysis ; Toxoplasma/*immunology/pathogenicity ; Toxoplasmosis, Animal/immunology/*prevention & control

Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A 51Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-alpha, IL-6, and IL-1beta, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.
Animals ; *Cell Death ; Chromium Radioisotopes/metabolism ; Cytokines/*secretion ; Humans ; Microglia/cytology/immunology/*physiology ; Microscopy ; Naegleria fowleri/*pathogenicity ; Rats ; Staining and Labeling

Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-alpha in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10+F4/80+ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.
Animals ; Antigens, Differentiation/analysis ; Clonorchis sinensis/*enzymology ; Colon/pathology ; Cystatins/*metabolism ; Cytokines/secretion ; Dextran Sulfate/toxicity ; Female ; Helminth Proteins/*metabolism ; Immunologic Factors/*metabolism ; Inflammation/chemically induced/*pathology ; Interleukin-10/analysis ; Intestines/*drug effects/pathology ; Lymph Nodes/immunology ; Macrophages/chemistry/*immunology ; Mice ; Mice, Inbred C57BL ; Severity of Illness Index ; Spleen/immunology

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.
Animals ; Antibodies, Helminth/blood ; Chemokine CCL11/biosynthesis ; Cytokines/biosynthesis ; Female ; Gene Expression Profiling ; Immunoglobulin E/blood ; Interleukin-13/secretion ; Interleukin-4/secretion ; Interleukin-5/secretion ; Interleukins/biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptor, PAR-2/*metabolism ; Th2 Cells/*immunology ; Trichinella spiralis/*immunology ; Trichinellosis/*immunology