Current Trends in Immunology最新文献

{"title":"Interleukin-6 neutralization prolongs corneal allograft survival.","authors":"Shilpa Kodati, Sunil K Chauhan, Yihe Chen, Parisa Emami-Naeini, Masahiro Omoto, Thomas H Dohlman, William Stevenson, Afsaneh Amouzegar, Gayathri Tummala, Daniel R Saban, Reza Dana","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The purpose of this study is to determine the effect of systemic blockade of Interleukin-6 (IL-6) on allosensitization, regulatory T cell frequencies and suppressive phenotype, and allograft survival rates in a mouse model of corneal transplantation. Allogeneic corneal transplantation was performed using C57BL/6 mice as donors and BALB/c mice as recipients. Graft recipients were injected daily with either anti-IL-6 antibody or an isotype control antibody (1.25 mg/ml) for the first 7 days and on alternate days thereafter until week 8 after transplantation. Allograft survival was evaluated for 8 weeks using Kaplan-Meier survival analysis. Draining lymph nodes (DLN) were harvested at week 3 after transplantation, and proliferation of isolated recipient T cells through direct and indirect pathways was determined using mixed lymphocyte reaction assay. Frequencies of CD4⁺CD25⁺Foxp3⁺ regulatory T cells, their expression of Foxp3, and frequencies of IFNy⁺CD4⁺ Th1 cells were determined in DLN using flow cytometry. Finally, CD4⁺ T cells were cultured with bone marrow-derived dendritic cells from either C57BL/6 or BALB/c mice in the presence of IL-6-blocking antibody to determine Treg induction through direct and indirect pathways, respectively. Treatment with anti-IL-6 antibody suppressed both the direct and indirect pathways of allosensitization in graft recipients and significantly improved allograft survival rates. Furthermore, <i>in vivo</i> blockade of IL-6 enhanced Foxp3 expression by Tregs in graft recipients undergoing rejection, but did not exert a significant effect on Treg frequencies. Finally, IL-6 neutralization <i>in vitro</i> enhanced the differentiation of Tregs from CD4⁺ T cells through both direct and indirect pathways. Our results demonstrate that systemic administration of IL-6-blocking antibody to corneal allograft recipients suppresses direct and indirect routes of allosensitization, is associated with increased expression of Foxp3 by Tregs, and improves allograft survival rates.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"19 ","pages":"105-113"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428205/pdf/nihms-1017623.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37085396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of metabolic reprogramming in T cell fate and function.","authors":"Nikolaos Patsoukis,&nbsp;Kankana Bardhan,&nbsp;Jessica Weaver,&nbsp;Christoph Herbel,&nbsp;Pankaj Seth,&nbsp;Lequn Li,&nbsp;Vassiliki A Boussiotis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>T lymphocytes undergo extensive changes in their metabolic properties during their transition through various differentiation states, from naïve to effector to memory or regulatory roles. The cause and effect relationship between metabolism and differentiation is a field of intense investigation. Many recent studies demonstrate the dependency of T cell functional outcomes on metabolic pathways and the possibility of metabolic intervention to modify these functions. In this review, we describe the basic metabolic features of T cells and new findings on how these correlate with various differentiation fates and functions. We also highlight the latest information regarding the main factors that affect T cell metabolic reprogramming.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"17 ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367635/pdf/nihms831124.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34867652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defective iron homeostasis in human immunodeficiency virus type-1 latency.","authors":"Hanxia Huang, Zhao-Hua Zhou, Rewati Adhikari, Kenneth M Yamada, Subhash Dhawan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Highly active antiretroviral therapy has significantly improved the life of HIV-1-infected individuals, yet complete eradication of HIV-1 reservoirs (i.e., latently infected cells) remains a major challenge. We have previously shown that induction of the endogenous cytoprotective enzyme heme oxygenase-1 (HO-1) by its natural substrate hemin reduces susceptibility of T cells and macrophages to HIV-1 infection. In the present study, we demonstrate that hemin treatment stimulated virus production by latently infected ACH-2 cells, followed by cellular toxicity and death when stimulated with TNF-α or co-cultured with monocyte-derived macrophages (MDM). This cytotoxicity was associated with low levels of the iron-binding protein ferritin and the iron transporter ferroportin with lack of hemoglobin catabolic enzyme HO-1, resulting in substantial iron accumulation in the activated ACH-2 cells. Defective iron homeostasis in ACH-2 cells provides a model system for selective targeting of the latent HIV-1 reservoir by hemin-induced iron toxicity.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"17 ","pages":"125-131"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562369/pdf/nihms842231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35333260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of the heme oxygenase-1 inducer hemin against Ebola virus infection.","authors":"Hanxia Huang, Krishnamurthy Konduru, Veronica Solovena, Zhao-Hua Zhou, Namita Kumari, Kazuyo Takeda, Sergei Nekhai, Sina Bavari, Gerardo G Kaplan, Kenneth M Yamada, Subhash Dhawan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Promising drugs to treat Ebola virus (EBOV) infection are currently being developed, but so far none has shown efficacy in clinical trials. Drugs that can stimulate host innate defense responses may retard the progression of EBOV disease. We report here the dramatic effect of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of EBOV replication. Treatment of primary monocyte-derived macrophages (MDM), Vero E6 cells, HeLa cells, and human foreskin fibroblasts (HFF1) with hemin reduced EBOV infection by >90%, and showed minimal toxicity to infected cells. Inhibition of HO-1 enzymatic activity and silencing HO-1 expression prevented the hemin-mediated suppression of EBOV infection, suggesting an important role for induction of this intracellular mediator in restricting EBOV replication. The inverse correlation between hemin-induced HO-1 and EBOV replication provides a potentially useful therapeutic modality based on the stimulation of an innate cellular response against Ebola infection.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"17 ","pages":"117-123"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging immunotherapeutics in adenocarcinomas: A focus on CAR-T cells.","authors":"Mahboubeh Yazdanifar, Ru Zhou, Pinku Mukherjee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>More than 80% of all cancers arise from epithelial cells referred to as carcinomas. Adenocarcinomas are the most common type of carcinomas arising from the specialized epithelial cells that line the ducts of our major organs. Despite many advances in cancer therapies, metastatic and treatment-refractory cancers remain the 2^nd leading cause of death. Immunotherapy has offered potential opportunities with specific targeting of tumor cells and inducing remission in many cancer patients. Numerous therapies using antibodies as antagonists or checkpoint inhibitors/immune modulators, peptide or cell vaccines, cytokines, and adoptive T cell therapies have been developed. The most innovative immunotherapy approach so far has been the use of engineered T cell, also referred to as chimeric antigen receptor T cells (CAR-T cells). CAR-T cells are genetically modified naïve T cells that express a chimeric molecule which comprises of the antigen-recognition domains (scFv) of an anti-tumor antibody and one, two, or three intracellular signaling domains of the T cell receptor (TCR). When these engineered T cells recognize and bind to the tumor antigen target <i>via</i> the scFv fragment, a signal is sent to the intracellular TCR domains of the CAR, leading to activation of the T cells to become cytolytic against the tumor cells. CAR-T cell therapy has shown tremendous success for certain hematopoietic malignancies, but this success has not been extrapolated to adenocarcinomas. This is due to multiple factors associated with adenocarcinoma that are different from hematopoietic tumors. Although many advances have been made in targeting multiple cancers by CAR-T cells, clinical trials have shown adverse effects and toxicity related to this treatment. New strategies are yet to be devised to manage side effects associated with CAR-T cell therapies. In this review, we report some of the promising immunotherapeutic strategies being developed for treatment of most common adenocarcinomas with particular emphasis on the future generation of CAR-T cell therapy.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"17 ","pages":"95-115"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484157/pdf/nihms869669.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35127119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme oxygenase-1-mediated host cell response inhibits the susceptibility of prostate cancer cells to retroviral infection and retards their proliferation.","authors":"Zhao-Hua Zhou,&nbsp;Namita Kumari,&nbsp;Jennifer Catalano,&nbsp;Sergei Nekhai,&nbsp;Jasen Wise,&nbsp;Kenneth M Yamada,&nbsp;Subhash Dhawan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Xenotropic murine leukemia virus-related virus (XMRV) resembles endogenous murine leukemia virus and was used in this study as a model for a new retrovirus infecting human cells. We demonstrate that induction of an HO-1-mediated host cell response inhibited the susceptibility of LNCaP prostate cancer cells to XMRV infection and efficiently retarded the growth of these prostate cancer cells. Our studies delineate a role of HO-1 in the host defense against retroviral infections and may provide novel therapeutic strategies for the treatment of HO-1-sensitive prostate cancer.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"14 ","pages":"53-56"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302767/pdf/nihms564211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33003046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current trends in negative immuno-synergy between two sexually transmitted infectious viruses: HIV-1 and HSV-1/2.","authors":"Aziz Alami Chentoufi, Xavier Dervillez, Pierre-Alain Rubbo, Tiffany Kuo, Xiuli Zhang, Nicolas Nagot, Edouard Tuaillon, Philippe Van De Perre, Anthony B Nesburn, Lbachir Benmohamed","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the current era of effective anti-retroviral therapy, immuno-compromised patients with HIV-1 infection do live long enough to suffer diseases caused by many opportunistic infections, such as herpes simplex virus type 1 and/or type 2 (HSV-1/2). An estimated two-third of the 40 million individuals that have contracted HIV-1 worldwide are co-infected with HSV-1/2 viruses, the causative agents of ocular oro-facial and genital herpes. The highest prevalence of HIV and HSV-1/2 infections are confined to the same regions of Sub-Saharan Africa. HSV-1/2 infections affect HIV-1 immunity, and vice versa. While important research gains have been made in understanding herpes and HIV immunity, the cellular and molecular mechanisms underlying the crosstalk between HSV-1/2 and HIV co-infection remain to be fully elucidated. Understanding the mechanisms behind the apparent HSV/HIV negative immuno-synergy maybe the key to successful HSV and HIV vaccines; both are currently unavailable. An effective herpes immunotherapeutic vaccine would in turn - indirectly - contribute in reducing HIV epidemic. The purpose of this review is: (i) to summarize the current trends in understanding the negative immuno-crosstalk between HIV and HSV-1/2 infections; and (ii) to discuss the possibility of developing a novel mucosal herpes immunotherapeutic strategy or even a combined or chimeric immunotherapeutic vaccine that simultaneously targets HIV and HSV-1/2 infections. These new trends in immunology of HSV-1/2 and HIV co-infections should become part of current efforts in preventing sexually transmitted infections. The alternative is needed to balance the ethical and financial concerns associated with the rising number of unsuccessful mono-valent clinical vaccine trials.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"13 ","pages":"51-68"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552495/pdf/nihms-421159.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31192904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons learned from studies of natural resistance in murine experimental autoimmune encephalomyelitis.","authors":"Harley Y Tse, Jinzhu Li, Xiaoqing Zhao, Fei Chen, Peggy P Ho, Michael K Shaw","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Experimental autoimmune encephalomyelitis (EAE) is a commonly-used animal model of the human demyelinating disease, multiple sclerosis (MS). Similar to MS, EAE is under genetic control in that certain mouse strains are susceptible to disease induction with myelin antigens, while other strains are resistant. In the past, major efforts studying EAE tended to focus on the mechanism of disease susceptibility pertaining to antigen specificities, disease progression and related cytokines. The basis of EAE resistance, on the other hand, had received relatively little attention. It is our contention that EAE resistance is a tightly regulated process and many lessons can be learned from studying its mechanisms. Initially, this laboratory showed that resistance to EAE induced by MBP in B6 mice and many other strains with different H-2 haplotypes could be reversed in an adoptive transfer system by challenging the recipients with MBP-CFA. The disease developed in these mice was very similar to that induced in EAE susceptible mouse strains without the antigenic challenge. This approach of reversing EAE resistance was confirmed by several other laboratories. It was also demonstrated definitively that EAE was mediated by the donor T cells and not by host T cells. Indeed, a \"resistant\" host environment did not affect the outcome of disease development. The antigenic challenge appeared to induce an anamnestic response in the donor T cells, as the antigen dose used could be as low as only 5µg per mouse. Significantly, the period between adoptive cell transfer and antigenic challenge could be as long as over one year, again indicating that the donor cells persisted in the host for a long period of time. Recently, it has been suggested that EAE resistance can be due to the activities of regulatory T cells (Tregs). Depletion of Tregs with anti-CD25 antibodies prior to immunization with PLP139-151 rendered 30% of resistant B10.S mice to develop EAE. These results were confirmed in SJL.B mice responding to MBP but not in B6 mice responding to the same antigen, suggesting that regulation might vary among EAE resistant mouse strains. In addition, it is noted that while B6 and SJL.B mice are resistant to EAE induction with MBP, these mice are susceptible to disease induction when immunized with MOG, suggesting that EAE susceptibility verses resistance is antigen dependent. This unique mouse model, coupled with advance technologies such as peptide/IA tetramers and microarrays, should provide a powerful tool for further elucidation of the basic mechanisms of EAE resistance.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"13 ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005425/pdf/nihms373003.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32315511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype and function of regulatory T cells in the genital tract.","authors":"Janina Jiang, Kathleen A Kelly","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>T cells with the specialized ability to suppress both adaptive and innate immune responses have been identified and called T regulatory cells (Tregs). The primary function of Tregs is to maintain a balance between immunity (foreign Ag) and tolerance (self Ag) to tissues. Tregs prevent autoimmune disease, maintain immune homeostasis and modulate protective responses against infection. Tregs function in two ways; 1) limiting the magnitude of effector responses which influence the adequate control of infection and 2) control collateral tissue damage caused by vigorous antimicrobial responses against pathogens. Initially, the immune suppressive ability of CD4 T cells was predicted by expression of the forkhead box p3 (Foxp3) transcription factor. However, many reports have demonstrated immune suppressive function in an array of other T cells which include iT(R)35, CD8+, NKT cells, especially in mucosal tissues. The immune suppressive mechanisms of Tregs include contact-dependent, cytokine secretion and regulation of immune cell migration. The expanded group of Tregs is crucial for protecting the function of mucosal tissues such as the gut, respiratory and genital tracts, as these tissues are routinely exposed to foreign pathogens.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"12 ","pages":"89-94"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266607/pdf/nihms332888.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30421371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why rethink the structure-function relationships regulating TCR behavior?","authors":"Melvin Cohn","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although the generally accepted (Standard) Model of the TCR has powered the accumulation of a large body of crucial data, it is lacking because of the failure of its basic tenet that allele-specific recognition of MHC-encoded restricting elements can be derived by somatic selection on a random repertoire. The limitations of the Standard Model due to this tenet and a glimpse at what a competing model might look like add up to yield a surprising new view of the structure-function relationships of the TCR. A published experiment illustrating this is discussed.</p>","PeriodicalId":34989,"journal":{"name":"Current Trends in Immunology","volume":"10 ","pages":"105-111"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345953/pdf/nihms241699.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30607270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}