• Molecules and Cells
• /
• 제43권11호
• /
• pp.921-934
• /
• 2020

Lck-interacting transmembrane adaptor 1 (LIME) has been previously identified as a raft-associated transmembrane protein expressed predominantly in T and B lymphocytes. Although LIME is shown to transduce the immunoreceptor signaling and immunological synapse formation via its tyrosine phosphorylation by Lck, a Src-family kinase, the in vivo function of LIME has remained elusive in the previous studies. Here we report that LIME is preferentially expressed in effector T cells and mediates chemokine-mediated T cell migration. Interestingly, in LIME^-/- mice, while T cell receptor stimulation-dependent proliferation, differentiation to effector T cells, cytotoxic T lymphocyte (CTL) function and regulatory T lymphocyte (Treg) function were normal, only T cell-mediated inflammatory response was significantly defective. The reduced inflammation was accompanied by the impaired infiltration of leukocytes and T cells to the inflammatory sites of LIME^-/- mice. More specifically, the absence of LIME in effector T cells resulted in the reduced migration and defective morphological polarization in response to inflammatory chemokines such as CCL5 and CXCL10. Consistently, LIME^-/- effector T cells were found to be defective in chemokine-mediated activation of Rac1 and Rap1, and dysregulated phosphorylation of Pyk2 and Cas. Taken together, the present findings show that LIME is a critical regulator of inflammatory chemokine-mediated signaling and the subsequent migration of effector T cells to inflammatory sites.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권13호
• /
• pp.5397-5400
• /
• 2015

Background: The aim of this study was to investigate the predictive value of white blood cells (WBC), the neutrophil to lymphocyte ratio (NLR), platelet indices including mean platelet volume (MPV), platelet distribution width (PDW), platelet crit (PCT) and platelet to lymphocyte ratio (PLR) in discrimination between benign and malign endometrial lesions, and early and advanced stage endometrial adenocarcinomas. Materials and Methods: Data for 105 patients undergoing total abdominal or vaginal hysterectomy for benign uterine diseases and 114 patients surgically staged for endometrium adenocarcinoma at Ondokuz Mayis University, Department of Gynecology and Obstetrics, between 2008 and 2014, were collected. Parameters were preoperative and postoperative complete blood counts in the week prior to surgery with differentials including WBC, platelet count, platelet indices (MPV, PCT, PDW), NLR and PLR. Pathologic evaluations for both benign and malign endometrium lesions, grade of endometrium adenocarcinoma, tumor stage, presence of lymphovascular space invasion (LVI) were retrospectively analyzed. Results: Regarding definitive factors in discriminating patients with endometrium cancer from those with benign diseases, MPV was significantly increased in the malign group whereas there was a significant decrease in the PDW value compared to the benign group. The best cut-off value in differentiation of the benign and malign groups, malign cases were found to increase over the value of 7.54 for MPV, and under 37.8 for PDW. When definitive factors in discrimination of early stage endometrium cancer from advanced stage disease and LVI in the malign group were evaluated according to the ROC analysis, no significant relation was detected between blood parameters and the stage and the LVI of the disease. Conclusions: MPV and PDW may have predictive value in the discrimination of benign and malign endometrium diseases. Nevertheless, since there have been few reports on this topic, further large-scale prospective studies are necessary.

• 대한이식학회지
• /
• 제32권4호
• /
• pp.84-91
• /
• 2018

Background: This study examined the outcomes of ABO incompatible living donor liver transplantation (LDLT). The changes in the immunologic factors that might help predict the long term outcomes were also studied. Methods: Twenty-three patients, who underwent ABO incompatible LDLT from 2010 to 2015, were reviewed retrospectively. The protocol was the same as for ABO compatible LDLT except for the administration of rituximab and plasma exchange. The clinical outcomes and immunologic factors, such as isoagglutinin titer and cluster of differentiation 20+ (CD20+) lymphocyte levels were reviewed. Results: The center showed a 3-year survival of 64% with no case of antibody-mediated rejection. When transplantation-unrelated mortalities (for example, traffic accidents and myocardial infarction) were removed from statistical analysis, the 3-year survival was 77.8%. Although isoagglutinin titers continued to remain at low levels, the CD20+ lymphocyte levels recovered to the pre-Rituximab levels at postoperative one year. Conclusions: As donor shortages continue, ABO incompatible liver transplantation is a feasible method to expand the donor pool. On the other hand, caution is still needed until more long-term outcomes are reported. Because CD20+ lymphocytes are recovered with time, more immunologic studies will be needed in the future.

• 한국임상수의학회지
• /
• 제28권4호
• /
• pp.399-402
• /
• 2011

In recent years, the mesenchymal stem cells (MSC) derived from various tissues have been widely tested for developing cell therapies, tissue repair and transplantation. Although there has been much interest in the immunomodulatory properties of MSC and their immunologic reactions following autologous, allogeneic and xenogenic transplantation of MSC in vivo, up to date, the expression of immunogenic markers, such as class I and II human leukocyte antigens (HLA), after differentiation of human umbilical cord blood (hUCB)-derived MSC has been poorly investigated and require extensive in vitro and in vivo testing. In this experiment, the expression of the HLA-ABC and HLA-DR on hUCB-derived MSC have been tested by immunocytochemical staining. The undifferentiated MSC were moderately stained for HLA-ABC but very weakly for HLA-DR. In order to investigate the inhibitory effect of allogeneic lymphocytes on proliferation of MSC, the MSC were cultured in the presence or absence of peripheral allogeneic lymphocytes stimulated with concanavalin A. The allogeneic lymphocytes did not significantly inhibit MSC proliferation. We conclude that hUCB-MSC expressed moderately class I HLA antigen while almost negatively class II HLA antigen. The MSC have an immunomodulatory effect which can suppress the allogeneic response of lymphocytes. These in vitro data suggest that allogeneic MSC derived from cord blood can be useful candidate for allogeneic cell therapy and transplantation without a major risk of rejection.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.307.2-308
• /
• 2002

Acharan sulfate. a new glycosaminoglycan(GAG) isolated from the giant African snail Achatina fulica. was shown to have antitumor activity in vivo. To elucidate the mechanisms for the antitumor activity. we examined its impact on professional antigen presenting cells such as macrophages and dendritic cells (DCs). Acharan sulfate stimulated cytokine production (TNF-a and IL -1b). nitric oxide release. and morphological changes in a dose dependent manner on a macrophage cell Line Raw 264.7 cells. The differentiation-inducing activity of acharan sulfate was examined on immature DCs. Immature DCs were generated from mouse bone marrow (BM) cells by culturing with GM-CSF and IL-4, and then stimulated with acharan sulfate. The resultant DCs were then examined for funcional and phenotypic properties. It was found that acharan sulfate could induce functional maturation of immature DCs as determined by increased allogenic mixed lymphocyte reaction (MLR) and IL-12 production. Phenotypic. analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2 and CD40 also confirmed that acharan sulfate could induce maturation of immature DCs. These results suggest that that the antitumor activity of acharan sulfate is at least in part due to activation adn induction of differentiation of professinal antigen presenting cells. (omitted)

• 대한수의학회지
• /
• 제24권2호
• /
• pp.195-199
• /
• 1984

The present observations were focussed mainly on the macroscopic and histopathological observation to polyps encountered on the stomach of 4-month-old pig, small intestine of 3-month-old pig and cecum of 9-month-old dog. The results were summarized as follows; 1. The polyps were gray or pink hemispherical shapes attached by the broad base to the gastrointestinal walls and were 3 to 8 mm in diameter and diffuse appearance. The surfaces of polyps were flat or indented and were ulcerated in some large polyps. 2. In histopathological findings, the polyps were nodules composed of lymphoid follicles, which were characterized by the differentiation and proliferation of the lymphoid cells in the lamina propria or submucosa of the gastrointestinal tract. The lymphoid nodules have the thin septa and thick capsules of the connective tissues, also comprised more numerous and larger sinus-like-blood vessels and more diffuse lymphoid cells in the peripheral zones than those in the central zones of nodules. In addition, the external surface of the polyps bulged toward the intestinal lumen were covered with the abnormal epithelium, or the degenerative and necrotic lymphocyte aggregates. 3. These polyps were considered as lymphoid polyps caused by the hyperplasia of the lymhoid follicles.

• BMB Reports
• /
• 제41권8호
• /
• pp.575-580
• /
• 2008

Thymocyte-specific transcriptional regulatory systems can be used to better understand the relationship between transcription and V(D)J recombination during early T cell development. In this study, we generated transgenic mice expressing the transactivator Gal4-VP16 or the Gal4 DNA binding domain (Gal4-DBD) under the control of the lck proximal promoter, which is only active in immature thymocytes. From these studies Gal4-VP16 and Gal4-DBD expression was shown to significantly alter thymic cellularity and differentiation without significantly changing the $CD3^+$ thymocyte distribution. Furthermore, the presence of Gal4-VP16 or Gal4-DBD in the transgenic thymocytes retarded the mobility of the Gal4 DNA binding motif as determined by a gel mobility shift assay, suggesting that the developmental alteration did not affect the functional property of the transgenic proteins. These results indicated that lck promoter-driven Gal4-VP16 or Gal4-DBD expression did not affect $CD3^+$ mature thymocytes, thus this system can be applied to study transcriptional regulation of transresponder genes in bigenic mouse model thymocytes.

• BMB Reports
• /
• 제52권12호
• /
• pp.718-727
• /
• 2019

Severe combined immunodeficiency (SCID) is a group of inherited disorders characterized by compromised T lymphocyte differentiation related to abnormal development of other lymphocytes [i.e., B and/or natural killer (NK) cells], leading to death early in life unless treated immediately with hematopoietic stem cell transplant. Functional NK cells may impact engraftment success of life-saving procedures such as bone marrow transplantation in human SCID patients. Therefore, in animal models, a T cell-/B cell-/NK cell+ environment provides a valuable tool for understanding the function of the innate immune system and for developing targeted NK therapies against human immune diseases. In this review, we focus on underlying mechanisms of human SCID, recent progress in the development of SCID animal models, and utilization of SCID pig model in biomedical sciences. Numerous physiologies in pig are comparable to those in human such as immune system, X-linked heritability, typical T-B+NK- cellular phenotype, and anatomy. Due to analogous features of pig to those of human, studies have found that immunodeficient pig is the most appropriate model for human SCID.

• BMB Reports
• /
• 제52권11호
• /
• pp.625-634
• /
• 2019

Severe combined immunodeficiency (SCID) is a group of inherited disorders characterized by compromised T lymphocyte differentiation related to abnormal development of other lymphocytes [i.e., B and/or natural killer (NK) cells], leading to death early in life unless treated immediately with hematopoietic stem cell transplant. Functional NK cells may impact engraftment success of life-saving procedures such as bone marrow transplantation in human SCID patients. Therefore, in animal models, a T cell-/B cell-/NK cell＋ environment provides a valuable tool for understanding the function of the innate immune system and for developing targeted NK therapies against human immune diseases. In this review, we focus on underlying mechanisms of human SCID, recent progress in the development of SCID animal models, and utilization of SCID pig model in biomedical sciences. Numerous physiologies in pig are comparable to those in human such as immune system, X-linked heritability, typical T-B＋NK- cellular phenotype, and anatomy. Due to analogous features of pig to those of human, studies have found that immunodeficient pig is the most appropriate model for human SCID.

• 한국임상수의학회지
• /
• 제25권4호
• /
• pp.268-273
• /
• 2008

For evaluation of immune stimulation effect of lacquer tree extracts, lymphocytes were counted by labeling of FITC-conjugated monoclonal antibody in the pheripheral blood of pigs that fed with a fodder supplemented by lacquer tree extracts. Populations of MHC-II+, CD4+, and CD8+T lymphocytes were increased more than 2% level after 1 week feed supply of the lacquer tree extracts. The increase of those T cells reached at maximum level after 2 weeks in the tested group. B lympyocytes with surface IgM were increased 5% after 1 week feed supply of the lacquer tree extracts, and their numbers reached maximum after 2 weeks in the tested group. For the assessment of cytotoxicity of the lacquer tree extracts, morphological changes were examined on the epithelial cells of small intestine from pigs fed with a fodder supplemented by 0.1 % lacquer tree extracts for 6 weeks (the tested group). Thin-sectioned tissue of small intestine was fixed with glutaraldehyde, then coated with gold particles, and the specimen was examined under scanning electron microscope. The villi on the mucus membrane of jejunum and ileum from the tested pigswere enlarged on the tip and were linked each other.