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Chemokines, by virtue of their ability to recruit immune cells into allografts, play critical roles in acute transplantation rejection. CCR9 and its ligand, CCL25, is one of the key regulators of thymocyte migration and maturation in normal and inflammatory conditions. Moreover, several studies have revealed that high expression of CCR9 and CCL25 participated in many kinds of diseases. However, the role of CCR9 in allograft rejection is still unclear. In this study, we established a murine skin transplantation model of acute rejection. Our findings showed that the proportion of CCR9-expressing T cells was significantly increased in the spleen of allotransplanted mice compared with syngeneic transplantation. Furthermore, expression of CCL25 in allograft was similarly increased. Neutralization of CCL25 by intravenous injection of anti-CCL25 monoclonal antibody significantly prolonged skin allograft survival, decreased the number of infiltrating cells, and simultaneously suppressed the chemotactic ability and the proliferation of the splenic T cells in response to allogeneic antigens. Finally, blockade of CCL25 also diminished the secretion of IFN-γ by splenic T cells. These studies indicated that CCR9/CCL25 was involved in acute transplantation rejection and anti-CCL25 strategies might be useful in preventing acute rejection.

The ability of human cells to defend against viruses originating from distant species has long been ignored. Owing to the pressure of natural evolution and human exploration, some of these viruses may be able to invade human beings. If their ‘fresh’ host had no defences, the viruses could cause a serious pandemic, as seen with HIV, SARS (severe acute respiratory syndrome) and avian influenza virus that originated from chimpanzees, the common palm civet and birds, respectively. It is unknown whether the human immune system could tolerate invasion with a plant virus. To model such an alien virus invasion, we chose TMV (tobacco mosaic virus) and used human epithelial carcinoma cells (HeLa cells) as its ‘fresh’ host. We established a reliable system for transfecting TMV-RNA into HeLa cells and found that TMV-RNA triggered autophagy in HeLa cells as shown by the appearance of autophagic vacuoles, the conversion of LC3-I (light chain protein 3-I) to LC3-II, the up-regulated expression of Beclin1 and the accumulation of TMV protein on autophagosomal membranes. We observed suspected TMV virions in HeLa cells by TEM (transmission electron microscopy). Furthermore, we found that TMV-RNA was translated into CP (coat protein) in the ER (endoplasmic reticulum) and that TMV-positive RNA translocated from the cytoplasm to the nucleolus. Finally, we detected greatly increased expression of GRP78 (78 kDa glucose-regulated protein), a typical marker of ERS (ER stress) and found that the formation of autophagosomes was closely related to the expanded ER membrane. Taken together, our data indicate that HeLa cells used ERS and ERS-related autophagy to defend against TMV-RNA.

The objective of this study was to examine the feasibility of detecting toxoplasmic brain lesions in a mouse model of cerebral toxoplasmosis by ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI). Toxoplasmosis encephalitis was induced in Kunming mice by intracerebral injection of Toxoplasma gondii tachyzoites. T-2- and T-2(*)-weighted MRI was performed 1, 3, 4, 5 and 6 days after infection before USPIO injection; immediately after USPIO injection; and 24 h later. A comparison of USPIO enhancement and Gd-DTPA enhancement was made in three toxoplasmic mice 4 days after infection. Hematoxylin and eosin staining and Prussian blue staining were performed to detect inflammatory reactions and presence of iron in and around the toxoplasmic brain lesions. Nonenhanced T-2-/T-2(*)-weighted imaging detected few abnormalities in the brain up to 5 days. Most mice developed prominent hydrocephalus at 6 days. Gd-DTPA-enhanced imaging showed prominent enhancement of the cerebral ventricles but revealed only few space-occupying lesions in the parenchyma. USPIO-enhanced T-2(*)-weighted imaging showed improved detection of toxoplasmic brain lesions that were invisible to nonenhanced T-2-/T-2(*)-weighted imaging and gadolinium-enhanced imaging. Most of the enhancing lesions showed nodular enhancement immediately after USPIO injection, some of which changed appearance 24 h later, having a ring enhancement at the outer rim. It can be concluded that USPIO enhancement of the toxoplasmic lesions may reflect blood-brain barrier impairment and/or inflammatory reactions associated with these lesions. USPIO-enhanced imaging may be used in combination with gadoliniumenhanced imaging to provide better characterization of toxoplasmic brain lesions and, potentially, improve the differential diagnosis of toxoplasmosis encephalitis. (c) 2007 Elsevier Inc. All rights reserved.

Corneal transplantation is one of the most common and successful transplant surgeries performed around the world. However, the high-risk corneal transplantation remains a high level of corneal graft failure. Gene transfer of immunomodulatory molecules is considered as one potential strategy in preventing allograft rejection. It is worthy evaluating the effects of the immunemodulating agent on corneal allograft rejection. The purpose of this paper is to investigate the effects and mechanisms of recombinant adeno-associated virus mediated transforming growth factor-beta1 (rAAV-TGF-beta1) on corneal allograft survival using a high-risk rat model after penetrating keratoplasty (PKP). The mean survival time (MST) of corneal grafts was observed and immuno-histochemical staining of TGF-beta1 and Ox-62 was performed in the study. The MST showed significant prolongation in the rAAV-TGF-beta1 group compared to the allograft group. The rejection index (RI) at day 10 revealed was significantly greater in the allograft group than that of the other two groups. Besides the increase of TGF-beta1, the expression of Ox-62 decreasing in rAAV-TGF-beta1 transplanted recipients was detected after transplantation. In short, treatment with rAAV-TGF-beta1 prolongs corneal allograft survival and inhibits the Ox-62 expression in grafts after high-risk PKP.

Lipopolysaccharide (LPS) plays an important role in the activation of innate immune cells, leading to secretion of proinflammatory factors and bridging the adaptive immune system. Exposing total mouse thymic cells culture to LPS induced a unique expression profile of cytokines (IL-17A, IL-17F, and IL-22) and the essential ROR-γt master transcription factor, which suggested a preferential differentiation of thymocytes towards the Th17 cell phenotype. Th17-polarizing molecules (IL-23, IL-23R, IL-6, and TGF-β) and IL-17A(+)CD4(+) thymocytes were also specifically produced by the in vitro LPS-stimulation of thymic cells. Furthermore, both the expression of Th17 differentiation-related molecules and the frequency of Th17 cells were significantly up-regulated with increasing doses of LPS, as evidenced by quantitative RT-PCR and flow cytometric analysis, respectively. The expressions and frequency reached maximum levels when LPS exposure had been maintained at an extremely high concentration (100 μg/mL) for 48 h. On the other hand, depletion of thymic dendritic cells (DCs) blocked the LPS-induced polarization of thymus-derived Th17 cell lineage. Addition of bone marrow-derived DCs (BMDCs) to the purified immature CD4(+) CD62L(low) thymocytes culture recovered the switch towards Th17 cells, which synergistically prompted the cytotoxic activity of CD8(+) T cells. Taken together, our data indicates that high doses of LPS can promote the differentiation of mouse thymus-derived Th17 cells by a mechanism involving components associated with mature DCs.

Type capital I, Ukrainian natural killer T cells (NKT cells), a subset of CD1d-restricted T cells with invariant Valphabeta TCR, are characterized by prompt production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation through the TCR complex. The rapid release of cytokines implies that type capital I, Ukrainian NKT cells may play a critical role in modulating the upcoming immune responses, such as anti-tumor response, protection against infection, and autoimmunity. As a bridge between innate and adaptive immunity, type capital I, Ukrainian NKT cells differentiate and mature upon stimulations to achieve and maintain a homeostasis. Orchestrating with other arms of adaptive immunity, type capital I, Ukrainian NKT cells show strong cytotoxic effects in response to various tumors in a direct and/or indirect manner(s). This review will focus primarily on type capital I, Ukrainian NKT cell development, homeostasis, and effector functions, especially in anti-tumor immunity, and followed by their potential applications in treatment of cancers.

CD8(+) natural killer T (NKT) cells from EBV-associated tumour patients are quantitatively and functionally impaired. EBV-induced CD8(+) NKT cells drive syngeneic T cells into a Th1-bias response to suppress EBV-associated malignancies. IL-4-biased CD4(+) NKT cells do not affect either syngeneic T cell cytotoxicity or Th cytokine secretion. Circulating mDC1 cells from patients with EBV-associated malignancies impair the production of IFN-gamma by CD8(+) NKT cells. In this study, we have established a human-thymus-SCID chimaera model to further investigate the underlying mechanism of EBV-induced CD8(+) NKT cells in suppressing EBV-associated malignancies. In the human-thymus-SCID chimera, EBV-induced CD8(+) NKT cells suppress EBV-associated malignancies in a manner dependent on the Th1-bias response and syngeneic CD3(+) T cells. However, adoptive transfer with CD4(+) NKT cells alone inhibits T cell immunity. Interestingly, CD4(+) NKT cells themselves secrete high levels of IL-2, enhancing the persistence of adoptively transferred CD8(+) NKT cells and T cells, thereby leading to a more pronounced T cell anti-tumour response in chimaeras co-transferred with CD4(+) and CD8(+) NKT cells. Thus, immune reconstitution with EBV-induced CD4(+) and CD8(+) NKT cells synergistically enhances T cell tumour immunity, providing a potential prophylactic and therapeutic treatment for EBV-associated malignancies.

The major histocompatibility complex (MHC) class I-related molecules A (MICA) is a stress-inducible cell surface antigen that is recognized by intestinal epithelial Vdelta1 gammadelta T cells, natural killer (NK) cells and CD8(+) T cells with NKG2D receptor participating in the immunological reaction in the intestinal mucosa. The present study aimed to investigate the functions of the MICA*A5.1 allele in the development of ulcerative colitis (UC) in the Chinese population. The microsatellite polymorphisms of MICA were genotyped in 124 unrelated Chinese patients with UC and 172 ethnically matched healthy controls using a semiautomatic fluorescently labelled polymerase chain reaction. MICA*A5.1-expressing Raji cells were generated by gene transfection. Cytotoxicity of NK cells to Raji cells expressing different MICA molecules was detected using the lactate dehydrogenase method. Soluble MICA in the culture supernatant was detected by enzyme-linked immunosorbent assay. The frequency of MICA*A5.1 was significantly higher in UC patients compared with the healthy controls (29.0% versus 17.4%, P = 0.001, corrected P = 0.005, OR = 1.936, 95% CI 1.310-2.863) and the frequency of a MICA*A5.1/A5.1 homozygous genotype was increased in UC patients (18.5% versus 7% in healthy controls, P = 0.0032, corrected P = 0.048, OR = 3.036, 95% CI 1.447-6.372). Raji cells with MICA*A5.1 expression produced more soluble MICA (t = 5.75, P < 0.01) than Raji cells with full-length MICA expression in culture supernatant. Raji cells with MICA*A5.1 expression were more resistant to killing by NK cells than Raji cells with full-length MICA expression. The MICA*A5.1 allele and MICA*A5.1/A5.1 genotype are significantly associated with Chinese UC patients in central China. MICA*A5.1 may play a role in the development of UC by producing more soluble MICA and resistance to NK cells.

We present a novel nuclear targeting nanoprobe based on peptide functionalized gold nanoparticles and its surface-enhanced Raman scattering (SERS) in living cells. For the first time, we probe an original SERS signal from the living cell nucleus by using high-selectivity functionalized gold nanoparticles. The gold nanoparticles conjugated with SV-40 large T nuclear localization signal (NLS) peptide successfully enter the cell nucleus after the incubation with Hela cells and deliver the spatially localized chemical information of the nucleus, as well as the signature of chemicals that intruded subsequently. This new targeted nanoprobe is a nontoxic, biocompatible method for biological research, provided with multiple functions comprising subcellular targeting, intracellular imaging, and real-time SERS detection.

Chronic urticaria (CU) imposes profound impairment on patient's quality of life. Our study was done to evaluate the clinical efficacy and safety of desloratadine combined with dipyridamole, which is a platelet adhesion inhibitor in the treatment of CU. A randomized study was done in 64 autoimmunity CU patients with positive autologous plasma skin test (APST): 34 patients as treatment and 30 controls. The treatment group was treated with desloratadine and dipyridamole, and the control group was treated with desloratadine only. The efficiency and side-effect were evaluated at the end of treatment. The levels of fragment F(1+2) were measured by enzyme-linked immunosorbent assay in all patients at pre- and post-treatment. The clinical effectiveness rates of treatment and control group were, respectively, 85.20% (21 cured, 8 obvious effectiveness) and 70% (14 cured, 7 obvious effectiveness); they have a significant difference (x = 4.09, P < 0.05). Before treatment, the weals and pruritus in the treatment and control group were, respectively, (1.74 +/- 0.90, 1.79 +/- 0.73) and (1.67 +/- 0.84, 1.73 +/- 0.78). After treatment, the weals and pruritus in treatment and control group were, respectively, (0.38 +/- 0.73, 0.58 +/- 0.89) and (0.67 +/- 0.96, 1.10 +/- 1.12). These findings provide new insights into the pathogenesis of CU and suggest new therapeutic opportunities for treating this disease.

A complex process including both the innate and acquired immune responses results in allograft rejection. Some chemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but also in facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage of the allogeneic response. This review focuses on the impact of these chemoattractant proteins on transplant outcome and novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokine receptors and/or their ligands.

We investigated CD19+CD34+ and CD19+CD34- B cells from cord blood (CB) and typical patients with B cell lineage acute and chronic lymphocytic leukemia (B-ALL and B-CLL) in terms of expression and functions of CXCR5/CXCL13 and CCR7/CCL19. CXCR5 and CCR7 were selectively frequent expressed on B-ALL, B-CLL and CB CD19+CD34+ B cells, but not on CD19+CD34- B cells. Instead of induction of impressive chemotactic responsiveness, CXCL13 and CCL19 together induced significant resistance to TNF-alpha-mediated apoptosis in B-ALL and B-CLL but not CB CD19+CD34+ B cells. B-ALL and B-CLL CD19+CD34+ B cells expressed elevated level of Paternally Expressed Gene 10 (PEG10), and CXCL13 and CCL19 together significantly up-regulated PEG10 expression in the cells. We found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulated PEG10 expression and function, subsequent stabilized caspase-3 and caspase-8 in B-ALL and B-CLL CD19+CD34+ B cells, and rescued the cells from TNF-alpha-mediated apoptosis. We suggested that normal lymphocytes, especially naive B and T cells, utilized CXCR5/CXCL13 and CCR7/CCL19 for migration, homing, maturation, and cell homeostasis as well as secondary lymphoid tissues organogenesis. Meanwhile certain malignant cells took advantages of CXCR5/CXCL13 and CCR7/CCL19 for infiltration, resistance to apoptosis, and inappropriate proliferation.

New structure low intensity x-ray image system is mainly made of plane plate mode x-ray intensifier of single proximity focus and CCD data acquisition and processing system. The paper explains the noise source and characteristic of the low intensity x-ray image system. By the system composition, the image noise source of low x-ray imaging system is constituted with quantum noise, particulate noise and dark noise of CCD. Then the compound methods of the "multi-frame mean + morphological transform filter" is submitted which deals with the imaging noise. Firstly, some frame images is superimposed, then mean image is calculated from those images, which is under the principle of noise non-correlation. Secondly, distinguishing with the conventional ways of morphological transformation filtering algorithm, the differential image information is referred to de-noising. Under the multi-scale morphological thought, the differential image which is obtained from the source image includes noise and some image details. After the noise of the differential image is cut off by the wavelet translation, the differential image is added to the last filtered image by the multi-scale morphological filter, then the clean image is achieved which has no noise but keeps the image details.