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Introduction Primary biliary cholangitis (PBC) is characterized by lymphocyte cell-induced immune destruction of cholangiole. However, the immunological characteristics of peripheral blood cells in PBC patients remain unknown. This study was designed to reveal the differences in the immunological characteristics between PBC patients and healthy adults. Methods We performed high-throughput sequencing to determine the TRB–CDR3 and IGH–CDR3 repertoires of T and B cells in 19 healthy controls and 29 PBC patients. Different immunological characteristics, such as distinctive complementarity determining region 3 (TRB–CDR3) lengths, usage bias of V and J segments, and random nucleotide addition were identified in PBC and healthy control (HC) groups. Results The diversity of TRB–CDR3 was significantly lower in the PBC group compared with the HC group. CDR3 and the N addition length distribution were significantly changed compared with the HC group. It appeared that the PBC group had more short N additions and the HC group had more long N additions in the TRB–CDR3 repertoire. The results also revealed a set of PBC-associated clonotypes compared with the HC group. Conclusion This study suggested that PBC is a complex autoimmune disease process with evidence of different TRB–CDR3 rearrangements compared with healthy adults that share IGH–CDR3 peptides with some autoimmune diseases. This new insight may contribute to a better understanding of the immune functions of PBC patients and benefit efficient applications of PBC diagnosis and treatments.

Background: The purpose of this meta-analysis is to compare the efficacy of tranexamic acid (TXA) versus placebo after a total shoulder arthroplasty (TSA). Methods: In April 2017, a systematic computer-based search was conducted in the databases of PubMed, Embase, Web of Science, Cochrane Library, and Google. Studies comparing TXA versus placebo in reducing blood loss after TSA were included. The endpoints were the need for transfusion, blood loss in drainage, hemoglobin drop, and total blood loss. Stata 12.0 software was used for the meta-analysis. Results: Six studies involving a total of 637 patients met the inclusion criteria. The meta-analysis revealed that, compared with control groups, treatment with TXA could decrease the need for transfusion (P

Allogeneic bone marrow transplantation (allo-BMT) is followed by a period of profound immune deficiency, which results in significant susceptibility to infections and limits the extensive application of this approach in clinic. Here, we transduced human interleukin-7 (IL-7) gene into donor-derived bone marrow stromal cells (MSCs) using adenovirus vector, and transplanted this gene-engineered MSCs (MSC-IL-7) into lethally irradiated C57BL/6 mice to investigate their effects on immune reconstitution following allo-BMT. Recipient mice receiving MSC-IL-7 cells plus T-cell-depleted bone marrow cells of BALB/c mice showed a significant increase in thymopoiesis and homeostatic expansion of peripheral T lymphocytes. Furthermore, injection of MSC-IL-7 cells following allo-BMT protected the host from the lethality caused by acute graft-versus-host disease (GVHD) and prevented the occurrence of GVHD induced by transplanted T cells. Thus, the use of MSC-IL-7 cells may be therapeutically useful for enhancing immune reconstitution without aggravating GVHD in allo-BMT mice.

Impaired immune reconstitution following allogeneic bone marrow transplantation (BMT) remains a major obstacle to its clinical application. In this study, interleukin (IL)-7-transduced bone marrow stromal cells (MSC-IL7, 1 x 10(6)/mouse) were transfused into lethally irradiated C57BL/6 recipient mice. By day 40 after transplantation, the recipient mice were challenged with the lymphoma cell line EL4. MSC-IL7 co-transplantation protected recipient mice from leukemic mortality (MST120 days after BMT vs mean survival time (MST) 70 days in the PBS group) It enhance the PFC count and DTH responses of recipients after transplantation. In conclusion, MSC mediated IL-7 gene therapy and may be a more feasible strategy to restore immune function following allo-TCD-BMT.

A mouse model of orthotopic bladder cancer simulating its human counterpart is of great importance in preclinical evaluation of new treatment modalities such as immunotxin therapy. The aim of the present study is to establish a novel nude mouse model with xenografted human bladder cancer.Single cell suspension of an established human bladder transitional cell carcinoma (TCC) cell line BIU-87 was instilled into nude mouse bladders which were pretreated with mild acid washing. The tumor growth in mouse bladder was assessed weekly by magnetic resonance imaging (MRI). At intervals following implantation and MRI tumor detection, the animals were sacrificed for necropsy, histological examination and immunocytochemical studies.The overall tumor establishment was 92.9% (52/56 mice) at 7 - 36 days, while in the subgroup of animals sacrificed at 12 - 13 days, 40 out of 42 animals (95.2%) developed TCC, the majority of which was superficial. The tumor stages were assessed by gross and histopathology. Histological examination confirmed the presence of grade II - III TCC. Immunocytochemistry confirmed that the tumor model maintained the biological and immunological features of BIU-87 cells. The changes seen on MRI images well correlated with the extent of tumor invasion identified by histology. Carcinoma in situ could be detected histologically at 7 - 9 days post-inoculation and progressed into papillary or invasive tumors thereafter.The orthotopic BIU-87 TCC model in nude mice is highly reproducible and is ideal for preclinical studies on experimental intravesical therapies.

To explore the role of anti-alphabeta T cell receptor (TCR) and anti-CD80 monoclonal antibodies (mAbs) combined with donor bone marrow cells (BMCs) infusion in the induction of murine skin allografts tolerance.On day 0, 2 x 10(8) BMCs of BALB/c mice were injected into recipient C57BL/6 mice via the tail vein, meanwhile, an intraperitoneal injection of TCRalphabeta mAb (500 microg) was given. On day 2, CD80 mAb was administered intraperitoneally. Skin grafting was performed on day 6. Delayed type hypersensitivity (DTH), mixed lymphocyte reaction (MLR), IL-2 reverse assay of MLR, adoptive transfer assay and chimerism detection were performed at different time points and tolerance mechanisms were investigated.The mean survival time (MST) of BALB/c skin allografts in C57BL/6 recipients that were treated by anti-TCRalphabeta and anti-CD80 mAbs combined with donor BMCs infusion was 70 days. DTH and MLR assay indicated that the tolerant mice displayed significant hyporesponsiveness. The result of IL-2 reverse test showed that clone anergy was probably involved in the formation of tolerance in the tolerant C57BL/6 mice. In vivo and in vitro adoptive transfer assay, suppressive activity in the spleens of tolerant C57BL/6 mice was observed. Chimerism existed in both the thymus and spleen of the tolerant C57BL/6 mice. The chimerism level gradually declined with time.Treatment of anti-TCRalphabeta and anti-CD80 mAbs combined with donor BMCs infusion can successfully induce a long-term tolerance in BALB/c mice to C57BL/6 skin graft. Multiple mechanisms, including clone anergy, suppressor cells and chimerism are involved in the tolerance.

To investigate the potential role of CTLA4Ig gene and OX40Ig protein in inducing transplantation tolerance and the mechanisms thereof.Thirty Lewis rats underwent transplantation of the hearts of DA rats and then randomly divided into five equal groups: control group, blank virus AdEGFP treated group (adenovirus containing EGFP at the dose of 1-5 x 10(9) pfu/ml was infused via portal vein immediately after the operation), AdCTLA4Ig treated group, AdOX40Ig treated group, and AdCTLA4Ig-IRES-OX40Ig treated group. The cardiac allograft survival was monitored by daily palpation. The total cessation of beating was defined as rejection and was confirmed by histology. Peripheral venous blood samples were collected 0, 3, 7, 10, 14, 21 and 28 days after the administration of adenovirus. ELISA was used to detect the expression of CTLA4Ig and OX40Ig. Twenty days after the heart transplantation single splenocyte suspension was prepared from surviving Lewis rats to be used as responder. The spleens of the normal donor-DA rats and the third strain DA rats to prepare single cell suspension of the same density to perform mixed lymphocyte reaction (MLR). Then recombinant IL-2 was added into the mixed MLR system to observe t\if the MLR could be reversed. Twenty days after the heart transplantation the splenocytes of the tolerating Lewis rats were injected into the lingual vein of the normal Lewis rats to observe the delayed type hypersensitivity (DTH) of the transferred Lewis rat to normal rat splenocytes. RT-PCR was used to detect the mRNA expression of IL-2, interferon-gamma, IL-4, and IL-10.The survival time of the AdCTLA4Ig-IRES-OX40Ig treated group was 151.5 d +/- 42.6 d, significantly longer than those of the AdOX40Ig treated group (60.2 d +/- 11.4 d (P = 0.003), AdCTLA4Ig (43.2 d +/- 11.1 d, P = 0.0026), control group (5.7 d +/- 0.5 d, P = 0.000 43), and AdEGFP treated group (5.2 d +/- 0.4 d, P = 0.000 43). CTLA4Ig and/or OX40Ig proteins were expressed at a high level in the adenoviral treated rats. Compared with the control group the splenocytes of the AdCTLA4Ig-IRES-OX40Ig, AdCTLA4Ig, and AdOX40Ig treated groups displayed donor-specific hyporesponsiveness (P = 0.0016, 0.0026 and 0.001), which could be partly reversed by the addition of exogenous IL-2. Moreover, the hyporesponsiveness could be transferred to the same strain rats through adoptive transfer. In comparison with the normal controls, the expression of Th1 type cytokines, such as IL-2 and IFN-gamma, was significantly decreased in the tolerating rats and significantly increased in the rats with rejection; however the expression of the Th2 type cytokines, such as IL03 and IL-10, was significantly increased in the tolerating rats and significantly decreased in the rats with rejection, showing a deviation of Th1/Th2 type cytokines.AdCTLA4Ig-IRES-OX40Ig-mediated genes transfer renders prolonged expression of CTLA4Ig and OX40Ig in Lewis recipient rats, leading to a long-term survival of cardiac allografts. The induced tolerance is donor-specific, and the mechanisms may be associated with T cell anergy, deviation of Th1/Th2, and the regulatory T cells.